Cosmetic Compositions Comprising at Least One Peptide with at Least One Immobilized Aromatic Cycle

ABSTRACT

Topical cosmetic use as a whitening active ingredient of at least one peptide, comprising at least one blocked aromatic cycle and having the general formula (I): A-(Xa)m-Xc-(Xb)n-B. The invention also discloses a cosmetic composition comprising at least said peptide and a method of decreasing skin pigmentation, whitening or lightening human skin, comprising a topical application of said composition.

This application claims benefit of Fr application No 0604070 filed May,5, 2006 and U.S. Provisional Application Ser. No. 60/789,514 filed May8, 2006. The above-mentioned applications are hereby incorporated byreference.

The present invention refers to the dermopharmaceutical field, and moreparticularly the cosmetic field. The present invention refers to the useof at least one peptide comprising at least one immobilized aromaticcycle and having the general formula (I) A-(Xa)m-Xc-(Xb)n-B in or forthe preparation of pharmaceutical, preferably dermopharmaceutical and/orcosmetic compositions, as an active, in particular in order to decreaseskin pigmentation, to lighten, to whiten or to bleach skin complexion orhomogenize skin color.

BACKGROUND OF THE INVENTION

Cosmetic industry is permanently seeking new ingredients possessing realactivities and which are available for topical use by the public.

For numerous persons, the desire to maintain or retrieve a youngappearance has made the fight against skin aging a major economic issue,hence an active research for new compounds, more and more effective inthis fight against deteriorated/damaged/imperfect skin.

The unsightliness of hyperpigmented spots, also called chloasma, melasmaor senescence spots, a long-time concern for women, is at the origin ofthe development of numerous cosmetic products with a lightening, evenwhitening purpose. However, in order to match the evolution of attitudestoward the global handling of skin pigmentation problems, it isnecessary to address today a larger public. Indeed, women but also men,young or less young, have always been worried by their complexion andtheir skin colour. In particular, Asian, African and South-Americancommunities often aspire to a more uniform, lighter complexion.

A large number of lightening ingredients, inhibitors of tyrosinase,based on a competitive inhibition of the enzyme responsible for thefabrication of melanin, or more complex products aimed either at theinhibition of the intracellular activation of the tyrosinase, or at theinhibition of the calcium fluxes decreasing the quantity of synthesizedmelanin or at other cellular mechanisms have not yielded resultssatisfactory enough. The discovery of the whitening activity of certainpeptides is the object of the present patent.

The application EP0389950 discloses a melanocyte-stimulating hormoneinhibitor having an amino acid sequence -His-Ser-Arg-Trp (SEQ ID NO 36)and its whitening effect. The application FR2761602 discloses peptidesequences His-Ser-Gln-Gly-Thr-Phe (SEQ ID NO 39),His-Ser-Gln-D-Ala-Thr-Phe (SEQ ID NO 37) and His-Ser-Gln-Ala-Thr-Phe(SEQ ID NO 52) which have lipolytic activity. The application EP1563826discloses a cosmetic treatment composition for keratinic mattercomprising oligopeptides with the sequence Tyr-Gly-Gly-Phe-Leu (SEQ IDNO 38) or His-Ser-Gln-Gly-Thr-Phe (SEQ ID NO 39). The applicationWO2005116067 discloses the MSH— agonist tripeptide His-DPhe-Trp-NH2 andits use for stimulating the melanisation. The application WO 2005/116068relates peptide A-His-DPhe-Arg-Trp-NH2 and its use for cosmeticallyfighting against canities. The application EP0972522 discloses abiologically functional peptide derivative of alpha-melanocytestimulating hormone having the sequence [(DL) Lip]His-D.homoPhe-Arg-Trp-NH2 (SEQ ID NO 40) and its cosmetic use to fightcutaneous disorders bound to an inflammation. The application FR2857581discloses a combination of a UV-B filter and an antiinflammatory agentHis-DPhe-Arg-Trp (SEQ ID NO 41) used to retard hair loss. Theapplication W 02/079146 discloses the compound His-Tic-piperidine andits use as modulator of melanocortin receptors.

One of the aim of the present invention is thus to be able to propose aproduct which presents an efficiency as a lightening agent, and sowithout important secondary effects.

SUMMARY OF THE INVENTION

Now, surprisingly, we have discovered that peptides containing at leastone immobilized aromatic cycle described hereinafter possess, in atopical application, cosmetical activities interesting as lighteningagents for the cosmetic treatment of diffuse or local hyperpigmentationand in general to decrease the melanogenesis in the human skin.

The object of this patent application rests in the discovery thatpeptides of the following structure (I) prove to be a new solution aslightening agents, (I) A-(Xa)m-Xc-(Xb)n-B, wherein A is H or N-acylgroup being biotin or an alkyl, aryl, aralkyl, acyl, alcohol, sulfonyl,sugar or alkoxy chain from 1 to 24 carbons, linear, or branched orcyclic, substituted or unsubstituted, saturated or unsaturated,hydroxylated or non-hydroxylated, sulfurated or non-sulfurated, whereinB is OR¹ or NR²R³; with R¹, R² and R³ independently either H, or analkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar or alkoxy chainfrom 1 to 24 carbons, linear, or branched or cyclic, substituted orunsubstituted, saturated or unsaturated, hydroxylated ornon-hydroxylated, sulfurated or non-sulfurated, wherein “m” and “n” arebetween 0 and 5 with the proviso that m+n≦5, wherein (Xa) and (Xb) areamino acid residues, which may be the same or different, geneticallyencoded or not encoded, and (Xa)m and (Xb)n are chains from 0 to 5 aminoacids (Xa1 Xa2 Xa3 Xa4 Xa5) (Xb1 Xb2 Xb3 Xb4 Xb5) which may be the sameor different, genetically encoded or not encoded, with the proviso thatm+n≦5, wherein Xc is an aromatic amino acid chosen on the following way:if Xa1=His, with the proviso that Xa2 is not Ser, Ala, Phe and nothomoPhe, preferably Xa2 is Leu, and that n=0 and m≦5 then Xc is an aminoacid residue selected among L- or D-Trp, L- or D-Phe, L- or D-Tyr, L- orD-Tic, L- or D-7-hydroxy-Tic or L- or D-Tpi; if Xa1=L-Tyr, m≦3 and n≦1,then Xc is an amino acid residue selected among L- or D-Trp, L- orD-Phe, L- or D-Tyr, L- or D-Tic, L- or D-7-hydroxy-Tic or L- or D-Tpiand, if Xa1 is not Tyr and not His, m and n chosen in a free way (withthe proviso that m+n≦5), then Xc is an amino acid residue selected amongL- or D-Tic or L- or D-7-hydroxy-Tic or L- or D-Tpi.

It has also been unexpectedly found that the sequenceTyr-Gly-Gly-Phe-Leu (SEQ ID NO 38), a fragment of endorphin calledenkephalin, possesses an inhibitive activity of the melanogenesis. Theendothelin which is a small protein also involved in the synthesis ofmelanin, and in a very similar way, peptidic fragments of endothelin, asfor example the hexapeptide His-Leu-Asp-Ile-Ile-Trp (SEQ ID NO 42) areeffective in this process.

Another aspect of the present invention is cosmetic ordermopharmaceutical compositions including at least one of said peptidecontaining at least one immobilized aromatic cycle and adermatologically acceptable carrier. It has now been discovered that theuse of at least one polypeptide in accordance with the present inventionin cosmetic, personal care or dermopharmaceutical compositions haswhitening and anti-aging activities. Anti-aging activity means somedegree or capacity for treating; preventing or ameliorating one or moresigns, symptoms and/or causes of skin aging.

Methods of using these cosmetics and dermopharmaceuticals to improve thestate and the appearance of human skin, and amongst others, to whitenthe skin, lighten the skin or unify the complexion, to regulate visibleand/or tactile discontinuities in skin associated, e.g. with skin aging,are also contemplated.

The present invention also is directed to the use of such compositionsfor the preparation of medicinal products useful for the treatment ofunwanted pigmentation, such as hyperpigmentation, as well as for methodsof their use in various cosmetic and dermatological applications.

DETAILED DESCRIPTION

All publications cited herein are hereby incorporated by reference intheir entirety.

All percentages and ratios used herein are by weight of the totalcomposition and all measurements made are at 25° C., unless otherwisedesignated.

The present invention refers to peptide having the general formulaA-(Xa)m-Xc-(Xb)n-B (I) and comprising at least one immobilized aromaticcycle.

According to a first aspect, the object of the present invention is atopical cosmetic use of at least one peptide, as a whitening activeingredient, comprising at least one immobilized aromatic cycle andhaving the general formula (I) A-(Xa)m-Xc-(Xb)n-B, wherein

-   -   a) A is H or N-acyl group being:    -   biotin or,    -   an alkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar or        alkoxy chain from 1 to 24 carbons, linear, or branched or        cyclic, substituted or unsubstituted, saturated or unsaturated,        hydroxylated or non-hydroxylated, sulfurated or non-sulfurated    -   b) B is OR¹ or NR²R³; with R¹, R² and R³ independently either:    -   H, or    -   an alkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar or        alkoxy chain from 1 to 24 carbons, linear, or branched or        cyclic, substituted or unsubstituted, saturated or unsaturated,        hydroxylated or non-hydroxylated, sulfurated or non-sulfurated    -   c) “m” and “n” are between 0 and 5 with the proviso that m+n≦5    -   d) (Xa) and (Xb) are amino acid residues, which may be the same        or different, genetically encoded or not encoded, and (Xa)m and        (Xb)n are chains from 0 to 5 amino acids (Xa1 Xa2 Xa3 Xa4 Xa5)        (Xb1 Xb2 Xb3 Xb4 Xb5) which may be the same or different        genetically encoded or not encoded, with the proviso that m+n≦5.    -   e) Xc is an aromatic amino acid chosen on the following way:        -   i. if Xa1=His, with the proviso that Xa2 is not Ser, Ala,            Phe and not homoPhe, preferably Xa2 is Leu, and that n=0 and            m then Xc is an amino acid residue selected among L- or            D-Trp, L- or D-Phe, L- or D-Tyr, L- or D-Tic, L- or            D-7-hydroxy-Tic or L- or D-Tpi,        -   ii. if Xa1=L-Tyr, m≦3 and n≦1, then Xc is an amino acid            residue selected among L- or D-Trp, L- or D-Phe, L- or            D-Tyr, L- or D-Tic, L- or D-7-hydroxy-Tic or L- or D-Tpi,        -   iii. if Xa1 is not Tyr and not His, m and n chosen in a free            way (with the proviso that m+n≦5), then Xc is an amino acid            residue selected among L- or D-Tic or L- or D-7-hydroxy-Tic            or L- or D-Tpi.

According to the present invention “immobilized aromatic cycle” meansthe presence of a more or less sterically immobilized (blocked) aromaticcycle within the peptide. This immobilization can be due to a chemicallinkage, such as in Tic (tetrahydroisoquinoline-3-carboxylic acid), itshydroxylated derivative (7-hydroxy-Tic) or Tpi (tryptoline-3-carboxylicacid), or to the group which constitutes the side chain of tryptophan(endothelin fragment), or to a steric configuration such as in spatialarrangement of enkephalin, wherein both cycles (side chains of tyrosineand phenylalanine) stabilize mutually in the space.

Compounds of general formula (I) may exist in free form or in the formof a salt formed with an acid that is acceptable in cosmetic terms. Thepresent invention includes both the free forms and the salts of thosecompounds.

According to the invention, the compounds of the formula (I) may formtogether with acids mono- or polyvalent, homogeneous or mixed salts,preferably with inorganic acids, or with appropriate organic aliphaticsaturated or unsaturated carboxylic acids, or with aromatic carboxylicacids, or with aromatic-aliphatic carboxylic acids, or withheteroaromatic carboxylic acids, or with aliphatic or aromatic sulfonicacids, preferably with acetic acid, lactic acid and/or chlorhydric acid.

In the context of the present invention, the term ‘acid acceptable incosmetic terms’ is taken to mean any non-toxic acid, including organicand inorganic acids. Such acids include acetic, para-aminobenzoic,ascorbic, aspartic, benzenesulfonic, benzoic, bismethylene salicylic,hydrobromic, hydrochloric, cinnamic, citraconic, citric,ethanedisulfonic, fumaric, gluconic, glutamic, glyconic, itaconic,lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, oxalic,palmitic, pamoic, pantothenic, phosphoric, propionic, salicylic,stearic, succinic, sulfamic, sulfuric, tartaric and para-toluenesulfonicacid. Hydrochloric acid and acetic acid are particularly preferred.

In the context of the present invention, the term ‘alkyl group’ is takento mean any alkyl group of 1 to 20 carbon atoms, linear or branched,substituted or not substituted (substituted, in particular, by analcohol, carboxylic acid or amine) and saturated or unsaturated. Inparticular, an alkyl group may be the methyl group.

In the context of the present invention, the term ‘aryl group’ is takento mean one or several aromatic rings, each consisting of 5 to 8 carbonatoms that may abut or be fused and may or may not be substituted. Inparticular, the aryl groups may be phenyl or naphthyl groups and thesubstituents, halogen atoms, alkoxy groups as defined above, alkylgroups as defined above or nitro groups.

In the context of the present invention, the term ‘aralkyl group’ istaken to mean any aryl group as defined above bonded via an alkyl groupas defined above. In particular, an aralkyl group is the benzyl group.

In the context of the present invention, the term ‘acyl group’ is takento mean any group —C═OR¹ in which R¹ may be an alkyl, aryl, aralkyl oramine group as defined above. In particular, an acyl group may be theacetyl group (R¹=—CH3).

In the context of the present invention, the term ‘amine group’ is takento mean any group —NR²R³ which R² and R³ may be the same or differentand each consists in a hydrogen atom or an alkyl, aryl, aralkyl, acyl,sulfonyl or sugar group as defined above.

In the context of the present invention, the term ‘sulfonyl group’, inthe context of the present invention, is taken to mean any group —SO₂R⁴,in which R⁴ may be an alkyl, aryl, aralkyl, alkoxy or amine group asdefined above. In particular, sulfonyl groups may be mesyl (R⁴=—CH3),triflyl (R⁴=—CF3) or tosyl (R⁴=-Ph-CH3) groups.

In the context of the present invention, the term ‘alkoxy group’, istaken to mean any —OR⁵ in which R⁵ may be an alkyl, aryl, aralkyl, acyl,sulfonyl or sugar group as defined above. In the context of the presentinvention, the term ‘sugar group’ is taken to mean any hexose, -ose or-oside group. In particular, the sugar groups may be glucose, arabinose,fructose, galactose, mannose, maltose, lactose, sucrose or cellobiosegroups.

The compounds of formula (I) may contain a center of asymmetry and thusexist in the form of optical isomers. The compounds according to thepresent invention are present as isomeric forms and mixture thereof, andas mixtures of rotamers.

As used herein, “peptide” and “polypeptide” refer to peptides which cancontain only genetically encoded amino acids, only not geneticallyencoded amino acids, or a combination of genetically encoded and notgenetically encoded amino acids. As used herein, the term “peptide”includes oligopeptide, peptide, polypeptide and derivatives thereof,peptide analogs and derivatives thereof, as well as dermatologicallyacceptable salts of these compounds. “Peptide analog” meanssynthetically modified amino acids or peptide, or a peptidic chain whosesequence presents homologies with the sequence of the similar referencepeptide, in other words in which 1 or several amino acids were replacedby one or some other amino acids. As used herein, “peptides” encompassalso complexes with other species such as metal ions (e.g., copper,zinc, manganese, magnesium, and the like).

The term “amino acid” as employed herein includes and encompasses all ofthe genetically encoded occurring, and non genetically encoded aminoacids, either in the D- or L-configuration if optically active.

Peptidic sequences are indicated herein using a traditional three letterconvention from left (N-terminal end) to right (C-terminal end). In thisnomenclature, -Ala is Alanine, -Asn is Asparagine, -Cys is Cysteine,-Gln is Glutamine, -Gly is Glycine, -Ile is Isoleucine, -Leu is Leucine,-Met is Methionine, -Phe is Phenylalanine, or its analogs, particularlya halogenated derivative, more particularly parafluoro-Phe, Homo-Phe,para-nitroPhe or phenylglycine, -Pro is Proline, -Ser is Serine, -Thr isThreonine, -Trp is Tryptophan, -Tyr is Tyrosine, -Val is Valine, -Asp isAspartic Acid, -Glu is Glutamic Acid, -Arg, is Arginine, -His is‘Histidine, -Lys is Lysine, -Orn is Ornithine, -Tic, is1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (ortetrahydroisoquinoline-3-carboxylic acid), -7-OH-Tic is7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, -Tpi is1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid (ortryptoline-3-carboxylic acid).

In a particular embodiment of this invention, the peptides arederivatives or fragments of the enkephalin (Tyr-Gly-Gly-Phe-Leu (SEQ IDNO 38)) and derivatives or fragments of the C terminal end of endothelin(His-Leu-Asp-Ile-Ile-Trp SEQ ID NO 42)). Analogues, incorporating aminoacids in the D configuration, for example, or derivatives of amino acidswith immobilized aromatic cycle are even more effective.

In order to enhance the bioavailability and cutaneous barrier crossingof those peptides, their lipophilicity or lipophilic character can beincreased either by acylation of the N-terminal NH2 group of thepeptide, by esterification of the carboxyl group with an alcohol, linearor branched, saturated or unsaturated, hydroxylated or not, or both.

In another preferred embodiment, the said acyl group is bound to theN-terminal end of at least one amino acid and is a straight-chain orbranched-chain, long or short chain, saturated or unsaturated,substituted with one or more hydroxyl, amino, acyl amino, sulfate orsulfide groups or may be unsubstituted, and which can be derived fromacetic acid, capric acid, lauric acid, myristic acid, octanoic acid,palmitic acid, stearic acid, behenic acid, linoleic acid, linolenicacid, lipoic acid, oleic acid, isostearic acid, elaidoic acid,2-ethylhexaneic acid, coconut oil fatty acid, tallow fatty acid,hardened tallow fatty acid, palm kernel oil fatty acid, lanolin fattyacid, biotinic acid, folic acid, decanoic acid, retinoic acid, sorbicacid, caproic acid, undecanoic acid, nicotinic acid, azelaic acid,propionic acid, butyric acid, valeric acid, lactic acid, malic acid ormixtures thereof.

In preferred methods of implementation of the invention, N-acyl groupsused are lauroyl (C₁₂) or myristoyl (C₁₄) or palmitoyl (C₁₆) or stearoyl(C₁₈) or oleoyl (C_(18:1)) or arachidic (C₂₀) or linoleoyl (C_(18:2)) orlipoyl or biotinyl (also called biotinoyl) or oleoyl or acetyl orelaidoyl or aleoyl or octanoyl. In a particularly preferred embodimentthe N terminal group is H, elaidoyl, myristoyl, biotinyl, octanoyl,steaoryl, acetyl or palmitoyl.

Peptides and derivatives in accordance with the present inventioninclude, without limitation: Pal-Tyr-Gly-Gly-Phe-Leu-OH (SEQ ID NO 1),Pal-Tyr-Gly-Gly-Phe-Pro-OH (SEQ ID NO 2), Pal-Tyr-Gly-Gly-Tic-Leu-OH(SEQ ID NO 3), Ac-7-OH-Tic-Gly-Gly-Phe-Leu-OH (SEQ ID NO 4),Step-Tyr-Gly-Gly-Tpi-Leu-OH (SEQ ID NO 5),Pal-His-Leu-Asp-Ile-Ile-Tpi-OH (SEQ ID NO 6),Ac-Tic-Leu-Asp-Ile-Ile-Trp-OH (SEQ ID NO 7), Boc-Leu-D-Trp-β-Ala-OH (SEQID NO 8), Pal-Tic-NH2 (SEQ ID NO 9), H-Ile-Lys-Tpi-OH (SEQ ID NO 10),Ac-Gly-7-OH-Tic-OH (SEQ ID NO 11), Pal-Leu-Leu-7-OH-Tic-NH2 (SEQ ID NO12), Ac-Tic-Gly-OH (SEQ ID NO 13), H-Tpi-Ile-OH (SEQ ID NO 14),H-Tpi-Ala-OH (SEQ ID NO 15), H-Tpi-Lys-OH (SEQ ID NO 16), H-Tpi-Phe-OH(SEQ ID NO 17), H-Tpi-Gly-OH (SEQ ID NO 18), H-Ile-Tpi-Lys-OH (SEQ ID NO19), Ac-Tic-Gly-Gly-Phe-Leu-OH (SEQ ID NO 20), Ac-7-OH-Tic-Gly-OH (SEQID NO 21), Pal-Tic-Leu-OH (SEQ ID NO 22), Pal-Tpi-NH2 (SEQ ID NO 23),Pal-Tpi-Gly-OH (SEQ ID NO 24), Pal-Tpi-Ile-OH (SEQ ID NO 25),Step-Tpi-Ile-OH (SEQ ID NO 26), Pal-His-Leu-Asp-Ile-Tpi-Ile-OH (SEQ IDNO 27), Pal-His-Leu-Asp-Ile-Ile-Trp-OH (SEQ ID NO 28),Pal-His-Leu-Asp-Ile-Ile-Phe-OH (SEQ ID NO 29),Ac-Phe-Leu-Asp-Ile-Ile-Trp-OH (SEQ ID NO 30),Step-Tyr-Gly-Gly-Trp-Leu-OH (SEQ ID NO 31),Biot-His-Leu-Asp-Ile-Ile-D-Trp-OH (SEQ ID NO 32), Lau-Leu-D-Trp-β-Ala-OH(SEQ ID NO 33), Ela-Tpi-OH (SEQ ID NO 34), Pal-D-7-hydroxy-Tic-OH (SEQID NO 35) or dermatologically acceptable salts of these compounds ormixtures thereof. “N-Pal” or “Pal” refers to an N-palmitoyl derivative.Likewise, “Step” refers to an N-stearoyl derivative, “Ac” refers to anN-acetyl derivative, “Ela” refers to an N-elaidoyl derivative.

The polypeptides of the present invention can be obtained by chemical orenzymatic synthesis from the constitutive amino acids or of theirderivatives; or is obtained by mild hydrolysis of natural proteins; orby biotechnology, or by vegetal extraction.

The present invention relates also to a cosmetic or dermopharmaceuticalcomposition comprising a safe and effective amount of at least onecompound of the general formula (I) defined herein and adermatologically acceptable carrier.

In one preferred aspect of the present invention, there is providedcompositions which comprise as a whitening active ingredient at leastone compound of the general formula (I) defined herein, and adermatologically acceptable carrier.

Peptides of general formula (I) are used in cosmetic anddermopharmaceutical compositions as per the invention at concentrationwhich may range from 0.00001% (w/w) to 100% (w/w), preferably between0.0001% (w/w) and 20% (w/w) and more preferably a concentration between0.001% and 5% (w/w) by weight of the composition. While thespecification concludes with the claims particularly pointing anddistinctly claiming the invention, it is believed that the presentinvention will be better understood from the following description. Theterms “having” and “including” are to be construed as open-ended unlessthe context suggests otherwise.

The compositions of the present invention can comprise or consistessentially of the components of the present invention as well as otheringredients described herein. As used herein, “consisting essentiallyof” means that the composition or component may include additionalingredients, but only if the additional ingredients do not materiallyalter the basic and novel characteristics of the claimed compositions ormethods. Preferably, such additives will not be present at all or onlyin trace amounts.

The term “dermatologically acceptable”, as used herein, means that thecompositions or components described are suitable for use in contactwith human skin without risk of toxicity, incompatibility, instability,allergic response, and the like.

All terms such as “skin aging”, “signs of skin aging”, “topicalapplication”, “skin whitening”, “loss of pigmentation” and the like areused in the sense in which they are generally and widely used in the artof developing, testing and marketing cosmetic and personal careproducts. The term “cosmetic composition” or more briefly just“composition” in accordance with the present invention relates to aformulation that can be used for cosmetic purposes, purposes of hygieneor as a basis for delivery of one or more dermopharmaceuticalingredients. This includes cosmetics, personal care products andpharmaceutical preparations. It is also possible that these formulationsare used for two or more of these same purposes at one time. A medicateddandruff shampoo, for example, has pharmacological properties and isused as a personal care product to provide clean hair.

“Signs of skin aging” and other phrases similarly referring to, forexample, symptoms of aging and the like include, but are not limited to,all outward visibly and tactilely perceptible manifestations as well asany other macro or micro effects due to skin aging. Such signs may beinduced or caused by intrinsic factors and/or extrinsic factors, e.g.,chronological aging and/or environmental damage. These signs may resultfrom processes which include, but are not limited to, the development oftextural discontinuities such as wrinkles and coarse deep wrinkles, skinlines, crevices, bumps, large pores (e.g., associated with adnexalstructures such as sweat gland ducts, sebaceous glands, or hairfollicles), or unevenness or roughness, loss of skin elasticity (lossand/or inactivation of functional skin elastin), sagging (includingpuffiness in the eye area and jowls), loss of skin firmness, loss ofskin tightness, loss of skin recoil from deformation, discoloration(including undereye circles), blotching, sallowness, hyperpigmented skinregions such as age spots and freckles, keratoses, abnormaldifferentiation, hyperkeratinisation, elastosis, collagen breakdown andother histological changes in the stratum corneum, dermis, epidermis,the skin vascular system (e.g., telangiectasia or spider vessels), andunderlying tissues, especially those proximate to the skin. As usedherein, the term “visible and/or tactile discontinuities in skin” mayencompass the stretch marks.

The composition according to the invention has the aim of decreasingpigmentation, in particular to lighten the complexion, attenuate senilelentigo, or homogenize skin color. In other words the present inventionrelates to cosmetic and dermatological composition for the prophylaxisand treatment of cosmetic or dermatological changes in skin, such as,for example, undesired pigmentation, for example local hyperpigmentationand incorrect pigmentation, the inhibition of natural pigmentation, orfor the purely cosmetic lightening of relatively large areas of skinwhich are quite appropriately pigmented for the individual skin type.

In certain preferred aspects, the composition according to the presentinvention useful as whitening and pigmentation reducing agent,preferably for the topical treatment of the human skin, preferably foreffectively reducing skin problems caused by pigmentation such as liverspots, freckles and dark complexion, is also used for improving thephysiological state and/or the physical appearance of human skin, inparticular to reduce, prevent or treat the signs of skin aging that aregenerated by sun exposure, physical and hormonal stress, abrasion,nutritional effects and other similar causes.

Some of the compositions of the present invention may also provideadditional benefits, including stability, absence of significant(consumer-unacceptable) skin irritation, anti-inflammatory activity andgood aesthetics

In a particular embodiment, the composition of the present inventioncontains further one or more one skin care active or additionalingredient selected from the group comprising: skin depigmenting agent,skin whitening agent, lightening or bleaching agent, optical brighteningagent, melanogenesis inhibitor agent, reducing pigmentation agent,keratolytic agent, desquamation agent, skin anti-aging agent,anti-wrinkle agent, anti-atrophy agent, anti-oxidant/radical scavengerand mixtures thereof. Examples of said skin care active or additionalingredient are, without limitation: tyrosinase inhibitor, protein kinaseA or C inhibitor, inhibitor of cellular calcium flux, inhibitor ofadrenergic receptors α or β, hydroquinone, arbutin, kojic acid and itsderivatives, vitamin C, vitamin E, vitamin A and their derivatives,boldine and its derivatives, licorice extract, citrus extract, bearberryextract, orange extract, lemon extract, cucumber extract, mulberryextract, rosemary extract, hops extract, mercaptosuccinic acid,mercaptodextran, glutathione, cysteine and its derivatives such asN-acetyl-L-cysteine, tocopherols, retinol, retinoic acid andretinaldehyde and mixtures.

“Adjuvants”, “additives”, and “optional components” are usedsynonymously with “additional ingredients”. “Skin care actives”,“actives” are used synonymously with “actives ingredients”.

I ADDITIVES

According to the invention, the dermatologically acceptable carrier canbe an aqueous or hydroalcoolic solution, a water in oil emulsion, an oilin water emulsion, a microemulsion, an aqueous gel, an anhydrous gel, aserum or a vesicle dispersion.

The compositions of the invention may include various other andadditional ingredients, which may be active, functional, conventionallyused in cosmetic, personal care or topical/transdermal pharmaceuticalproducts or otherwise. Of course, a decision to include an additionalingredient and the choice of specific additional ingredients depends onthe specific application and product formulation. Also, the line ofdemarcation between an “active” ingredient and an “inactive ingredient”is artificial and dependent on the specific application and producttype. A substance that is an “active” ingredient in one application orproduct may be a “functional” ingredient in another, and vice versa.

Thus, the compositions of the invention may include at least one skincare active. As used herein, “skin care actives” are additionalingredients, which provide some benefit to the object of thecomposition. Such additional ingredients may include one or moresubstances such as, without limitations, cleaning agents, hairconditioning agents, skin conditioning agents, hair styling agents,antidandruff agents, hair growth promoters, perfumes, sunscreen and/orsunblock compounds, pigments, moisturizers, film formers, hair colors,make-up agents, detergents, pharmaceuticals, thickening agents,emulsifiers, humectants, emollients, antiseptic agents, deodorantactives, dermatologically acceptable carriers and surfactants.

In any embodiment of the present invention, however, the actives usefulherein can be categorized by the benefit they provide or by theirpostulated mode of action. However, it is to be understood that theactives useful herein can in some instances provide more than onebenefit or operate via more than one mode of action. Therefore,classifications herein are made for the sake of convenience and are notintended to limit the active to that particular application orapplications listed.

In a preferred embodiment, where the composition is to be in contactwith human keratinous tissue, the additional ingredients should besuitable for application to keratinous tissue, that is, whenincorporated into the composition they are suitable for use in contactwith human keratinous tissue (hair, nails, skin, lips) without unduetoxicity, incompatibility, instability, allergic response, and the likewithin the scope of sound medical judgment.

The CTFA Cosmetic Ingredient Handbook, Tenth Edition (published by theCosmetic, Toiletry, and Fragrance Association, Inc., Washington, D.C.)(2004) describes a wide variety of nonlimiting materials that can beadded to the composition herein. Examples of actives which may be added,include, but are not limited to: skin soothing and healing agents, skinanti-aging agents, skin moisturizing agents, anti-wrinkle agents,anti-atrophy agents, skin smoothing agents, antibacterial agents,antifungal agents, pesticides, anti parasitic agents, antimicrobialagents, anti-inflammatory agents, anti-pruriginous agents, externalanaesthetic agents, antiviral agents, keratolytic agents, free radicalsscavengers, antiseborrheic agents, antidandruff agents, the agentsmodulating the differentiation, proliferation or pigmentation of theskin and agents accelerating penetration, desquamating agents,depigmenting or propigmenting agents, antiglycation agents, tighteningagents, agents stimulating the synthesis of dermal or epidermalmacromolecules and/or preventing their degradation; agents stimulatingthe proliferation of fibroblasts and/or keratinocytes or stimulating thedifferentiation of keratinocytes; muscle relaxants; antipollution and/oranti-free radical agents; slimming agents, anticellulite agents, agentsacting on the microcirculation; agents acting on the energy metabolismof the cells; cleaning agents, hair conditioning agents, hair stylingagents, hair growth promoters, sunscreen and/or sunblock compounds,make-up agents, detergents, pharmaceutical drugs, emulsifiers,emollients, antiseptic agents, deodorant actives, dermatologicallyacceptable carriers, surfactants, abrasives, absorbents, aestheticcomponents such as fragrances, colorings/colorants, essential oils, skinsensates, cosmetic astringents, anti-acne agents, anti-caking agents,anti foaming agents, antioxidants, binders, biological additives,enzymes, enzymatic inhibitors, enzyme-inducing agents, coenzymes, plantextracts, plant derivatives, plant tissue extracts, plant seed extracts,plant oils, botanicals, botanical extracts, ceramides, peptides,buffering agents, bulking agents, chelating agents, chemical additives,colorants, cosmetic biocides, denaturants, drug astringents, externalanalgesics, film formers or materials, e.g., polymers, for aiding thefilm-forming properties and substantivity of the composition, quaternaryderivatives, agents increasing the substantivity, opacifying agents, pHadjusters, pH regulator (e.g. triethanolamine), propellants, reducingagents, sequestrants, skin bleaching and lightening agents, skin tanningagents, skin-conditioning agents (e.g., humectants, includingmiscellaneous and occlusive), skin soothing and/or healing agents andderivatives, skin treating agents, thickeners, lipid thickener (e.g.stearic acid), vitamins and derivatives thereof, peeling agents,moisturizing agents, curative agents, lignans, preservatives (e.g.phoxyethanol and parabens), UV absorbers, a cytotoxic, ananti-neoplastic agent, a fat-soluble active, suspending agents,viscosity modifiers, dyes, non-volatile solvents, diluents, pearlescentaids, foam boosters, a vaccine, a water-soluble sunscreen,antiperspirant, depilatory, perfumed water, fat soluble sunscreenssubstance intended to improve the state of dry or aged skin, skinrestructuring agent (e.g. Siegesbeckia orientalis extract), emollient(e.g. C12-15 alkyl benzoate), excipients, fillers, minerals,anti-mycobacterial agents, anti-allergenic agents, H1 or H2antihistamines, anti-irritants, immune system boosting agents, immunesystem suppressing agents, insect repellents, lubricants, stainingagents, hypopigmenting agents, preservatives, photostabilizing agentsand their mixture.

Said additional ingredient is selected from the group consisting ofsugar amines, glucosamine, D-glucosamine, N-acetyl glucosamine,N-acetyl-D-glucosamine, mannosamine, N-acetyl mannosamine,galactosamine, N-acetyl galactosamine, vitamin B3 and its derivatives,niacinamide, sodium dehydroacetate, dehydroacetic acid and its salts,phytosterols, salicylic acid compounds, hexamidines, dialkanoylhydroxyproline compounds, soy extracts and derivatives, equol,isoflavones, flavonoids, phytantriol, farnesol, geraniol, peptides andtheir derivatives, di-, tri-, tetra-, penta-, and hexapeptides and theirderivatives, lys-thr-thr-lys-ser (SEQ ID NO 43),palmitoyl-lys-thr-thr-lys-ser (SEQ ID NO 49), carnosine, N-acyl aminoacid compounds, retinoids, retinyl propionate, retinol, retinylpalmitate, retinyl acetate, retinal, retinoic acid, water-solublevitamins, ascorbates, vitamin C, ascorbic acid, ascorbyl glucoside,ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbylphosphate, vitamins their salts and derivatives, provitamins and theirsalts and derivatives, ethyl panthenol, vitamin B, vitamin Bderivatives, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin K,vitamin K derivatives, pantothenic acid and its derivatives, pantothenylethyl ether, panthenol and its derivatives, dexpanthenol, ethylpanthenol, biotin, amino acids and their salts and derivatives, watersoluble amino acids, asparagine, alanine, indole, glutamic acid, waterinsoluble vitamins, vitamin A, vitamin E, vitamin F, vitamin D, mono-,di-, and tri-terpenoids, beta-ionol, cedrol, and their derivatives,water insoluble amino acids, tyrosine, tryptamine, butylatedhydroxytoluene, butylated hydroxyanisole, allantoin, tocopherolnicotinate, tocopherol, tocopherol esters, palmitoyl-gly-his-lys,phytosterol, hydroxy acids, glycolic acid, lactic acid, lactobionicacid, keto acids, pyruvic acid, phytic acid, lysophosphatidic acid,stilbenes, cinnamates, resveratrol, kinetin, zeatin,dimethylaminoethanol, natural peptides, soy peptides, salts of sugaracids, Mn gluconate, Zn gluconate, particulate materials, pigmentmaterials, natural colors, piroctone olamine,3,4,4′-trichlorocarbanilide, triclocarban, zinc pyrithione,hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate,ascorbyl glucoside, pyridoxine, aloe vera, terpene alcohols, allantoin,bisabolol, dipotassium glycyrrhizinate, glycerol acid, sorbitol acid,pentaerythritol acid, pyrrolidone acid and its salts, dihydroxyacetone,erythrulose, glyceraldehyde, tartaraldehyde, clove oil, menthol,camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazeldistillate, eicosene and vinyl pyrrolidone copolymers, iodopropylbutylcarbamate, a polysaccharide, an essential fatty acid, salicylate,glycyrrhetinic acid, carotenoïdes, ceramides and pseudo-ceramides, alipid complex, oils in general of natural origin such Shea butter,apricot oil, onagre oil, prunus oil, palm oil, monoi oil, HEPES;procysteine; O-octanoyl-6-D-maltose; the disodium salt ofmethylglycinediacetic acid, steroids such as diosgenin and derivativesof DHEA; N-ethyloxycarbonyl-4-para-aminophenol, bilberry extracts;phytohormones; extracts of the yeast Saccharomyces cerevisiae; extractsof algae; extracts of soybean, lupin, maize and/or pea; alverine and itssalts, in particular alverine citrate, extract of butcher's broom and ofhorse chestnut, and mixtures thereof, without this list being limiting.

Further skin care and hair care active ingredients that are particularlyuseful in combination with peptide of the general formula (I) can befound in SEDERMA commercial literature and on the website www.sederma.fr(herewith incorporated in its entirety).

In any embodiment of the present invention, however, the additionalingredients useful herein can be categorized by the benefit they provideor by their postulated mode of action. However, it is to be understoodthat the additional ingredients useful herein can in some instancesprovide more than one benefit or operate via more than one mode ofaction. Therefore, classifications herein are made for the sake ofconvenience and are not intended to limit the additional ingredients tothat particular application or applications listed.

1. Sugar Amines (Amino Sugars)

The compositions of the present invention can comprise a sugar amine,which is also known as amino sugar. Sugar amine compounds useful in thepresent invention can include those described in PCT Publication WO02/076423 and U.S. Pat. No. 6,159,485. In one embodiment, thecomposition comprises from about 0.01% to about 15%, more preferablyfrom about 0.1% to about 10%, and even more preferably from about 0.5%to about 5% by weight of the composition, of sugar amine.

Sugar amines can be synthetic or natural in origin and can be used aspure compounds or mixtures of compounds (e.g., extracts from naturalsources or mixtures of synthetic materials). For example, glucosamine isgenerally found in many shellfish and can also be derived from fungalsources. As used herein, “sugar amine” includes isomers and tautomers ofsuch and its salts (e.g., HCl salt) and is commercially available fromSigma Chemical Co.

Examples of sugar amines that are useful herein include glucosamine,N-acetyl glucosamine, mannosamine, N-acetyl mannosamine, galactosamine,N-acetyl galactosamine, their isomers (e.g., stereoisomers), and theirsalts (e.g., HCl salt). Preferred for use herein are glucosamine,particularly D-glucosamine and N-acetyl glucosamine, particularlyN-acetyl-D-glucosamine.

2. Vitamin B3 Compounds

The compositions of the present invention can include a vitamin B3compound. Vitamin B3 compounds are particularly useful for regulatingskin conditions, as described in U.S. Pat. No. 5,939,082. In oneembodiment, the composition comprises from about 0.001% to about 50%,more preferably from about 0.01% to about 20%, even more preferably fromabout 0.05% to about 10%, and still more preferably from about 0.1% toabout 7%, even more preferably from about 0.5% to about 5%, by weight ofthe composition, of the vitamin B3 compound.

As used herein, “vitamin B3 compound” means a compound having theformula:

wherein R is —CONH₂ (i.e., niacinamide), —COOH (i.e., nicotinic acid) or—CH₂OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of anyof the foregoing.

Exemplary derivatives of the foregoing vitamin B3 compounds includenicotinic acid esters, including non-vasodilating esters of nicotinicacid (e.g, tocopherol nicotinate, myristyl nicotinate), nicotinyl aminoacids, nicotinyl alcohol esters of carboxylic acids, nicotinic acidN-oxide and niacinamide N-oxide.

Suitable esters of nicotinic acid include nicotinic acid esters ofC1-C22, preferably C1-C16, more preferably C1-C6 alcohols.Non-vasodilating esters of nicotinic acid include tocopherol nicotinateand inositol hexanicotinate; tocopherol nicotinate is preferred.

Other derivatives of the vitamin B3 compound are derivatives ofniacinamide resulting from substitution of one or more hydrogens of theamide group. Specific examples of such derivatives include nicotinuricacid (C₈H₈N₂O₃) and nicotinyl hydroxamic acid (C₆H₆N₂O₂).

Exemplary nicotinyl alcohol esters include nicotinyl alcohol esters ofthe carboxylic acids salicylic acid, acetic acid, glycolic acid,palmitic acid and the like. Other non-limiting examples of vitamin B3compounds useful herein are 2-chloronicotinamide, 6-aminonicotinamide,6-methylnicotinamide, n-methyl-nicotinamide, n,n-diethylnicotinamide,n-(hydroxymethyl)-nicotinamide, quinolinic acid imide, nicotinanilide,n-benzylnicotinamide, n-ethylnicotinamide, nifenazone, nicotinaldehyde,isonicotinic acid, methyl isonicotinic acid, thionicotinamide,nialamide, 1-(3-pyridylmethyl)urea, 2-mercaptonicotinic acid, nicomol,and niaprazine.

Examples of the above vitamin B3 compounds are well known in the art andare commercially available from a number of sources, e.g., the SigmaChemical Company; ICN Biomedicals, Inc. and Aldrich Chemical Company.

One or more vitamin B3 compounds may be used herein. Preferred vitaminB3 compounds are niacinamide and tocopherol nicotinate. Niacinamide ismore preferred. When used, salts, derivatives, and salt derivatives ofniacinamide are preferably those having substantially the same efficacyas niacinamide.

Salts of the vitamin B3 compound are also useful herein. Nonlimitingexamples of salts of the vitamin B3 compound useful herein includeorganic or inorganic salts, such as inorganic salts with anionicinorganic species (e.g., chloride, bromide, iodide, carbonate,preferably chloride), and organic carboxylic acid salts (includingmono-, di- and tri-C1-C18 carboxylic acid salts, e.g., acetate,salicylate, glycolate, lactate, malate, citrate, preferablymonocarboxylic acid salts such as acetate). These and other salts of thevitamin B3 compound can be readily prepared by the skilled artisan(<<The Reaction of L-Ascorbic and D-Iosascorbic Acid with Nicotinic Acidand Its Amide”, J. Organic Chemistry, Vol. 14, 22-26 (1949)).

The vitamin B3 compound may be included as the substantially purematerial, or as an extract obtained by suitable physical and/or chemicalisolation from natural (e.g., plant) sources. The vitamin B3 compound ispreferably substantially pure, more preferably essentially pure.

3. Dehydroacetic Acid (DHA)

The composition of this invention can include dehydroacetic acid, havingthe structure:

or pharmaceutically acceptable salts, derivatives or tautomers thereof.The technical name for dehydroacetic acid is3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione and can be commerciallypurchased from Lonza.

Pharmaceutically acceptable salts include alkali metal salts, such assodium and potassium; alkaline earth metal salts, such as calcium andmagnesium; non-toxic heavy metal salts; ammonium salts; andtrialkylammonium salts, such astrimethylammonium and triethylammonium.Sodium, potassium, and ammonium salts of dehydroacetic acid arepreferred. Highly preferred is sodium dehydroacetate which can bepurchased from Tri-K, as Tristat SDHA. Derivatives of dehydroacetic acidinclude, but are not limited to, any compounds wherein the CH₃ groupsare individually or in combination replaced by amides, esters, aminogroups, alkyls, and alcohol esters. Tautomers of dehydroacetic acid canbe described as having the chemical formula C₈H₈O₄ and generally havingthe structure above.

In one embodiment, the compositions of the present invention cancomprise from about 0.001% to about 25% by weight of the composition,preferably from about 0.01% to about 10%, more preferably from about0.05% to about 5%, and even more preferably from about 0.1% to about 1%,of dehydroacetic acid or pharmaceutically acceptable salts, derivativesor tautomers thereof.

4. Phytosterol

The compositions of the present invention can comprise a phytosterol.For example, one or more phytosterols can be selected from the groupconsisting of β-sitosterol, campesterol, brassicasterol,Δ5-avennasterol, lupenol, α-spinasterol, stigmasterol, theirderivatives, analogs, and combinations thereof. More preferably, thephytosterol is selected from the group consisting of β-sitosterol,campesterol, brassicasterol, stigmasterol, their derivatives, andcombinations thereof. More preferably, the phytosterol is stigmasterol.

Phytosterols can be synthetic or natural in origin and can be used asessentially pure compounds or mixtures of compounds (e.g., extracts fromnatural sources). Phytosterols are generally found in the unsaponifiableportion of vegetable oils and fats and are available as free sterols,acetylated derivatives, sterol esters, ethoxylated or glycosidicderivatives. More preferably, the phytosterols are free sterols. As usedherein, “phytosterol” includes isomers and tautomers of such and iscommercially available from Aldrich Chemical Company, Sigma ChemicalCompany and Cognis.

In one embodiment, the composition of the present invention comprisesfrom about 0.0001% to about 25%, more preferably from about 0.001% toabout 15%, even more preferably from about 0.01% to about 10%, stillmore preferably from about 0.1% to about 5%, and even more preferablyfrom about 0.2% to about 2% of phytosterol, by weight of thecomposition.

5. Salicylic Acid Compound

The compositions of the present invention may comprise a salicylic acidcompound, its esters, its salts, or combinations thereof. In oneembodiment of the compositions of the present invention, the compositionpreferably comprises from about 0.0001% to about 25%, more preferablyfrom about 0.001% to about 15%, even more preferably from about 0.01% toabout 10%, still more preferably from about 0.1% to about 5%, and evenmore preferably from about 0.2% to about 2%, by weight of thecomposition, of salicylic acid compound.

6. Hexamidine

The compositions of the present invention can include hexamidinecompounds, its salts, and derivatives.

In one embodiment, the composition comprises from about 0.0001% to about25%, more preferably from about 0.001% to about 10%, more preferablyfrom about 0.01% to about 5%, and even more preferably from about 0.02%to about 2.5% of hexamidine by weight of the composition.

As used herein, hexamidine derivatives include any isomers and tautomersof hexamidine compounds including but not limited to organic acids andmineral acids, for example sulfonic acid, carboxylic acid, etc.Preferably, the hexamidine compounds include hexamidine diisethionate,commercially available as Eleastab® HP100 from LaboratoiresSerobiologiques.

7. Dialkanoyl Hydroxyproline Compounds

The compositions of the present invention can comprise one or moredialkanoyl hydroxyproline compounds and their salts and derivatives.

In one embodiment, the dialkanoyl hydroxyproline compounds arepreferably added to the composition from about 0.01% to about 10%, morepreferably from about 0.1% to about 5%, even more preferably from about0.1% to about 2% by weight of the composition Suitable derivativesinclude but are not limited to esters, for example fatty esters,including, but not limited to tripalmitoyl hydroxyproline and dipalmitylacetyl hydroxyproline. A particularly useful compound is dipalmitoylhydroxyproline. As used herein, dipalmitoyl hydroxyproline includes anyisomers and tautomers of such and is commercially available under thetradename Sepilift DPHP® from Seppic, Inc. Further discussion ofdipalmitoyl hydroxyproline appears in PCT Publication WO 93/23028.Preferably, the dipalmitoyl hydroxyproline is the triethanolamine saltof dipalmitoyl hydroxyproline.

8. Flavonoids

The compositions of the present invention can comprise a flavonoidcompound. Flavonoids are broadly disclosed in U.S. Pat. No. 5,686,082.As used herein, “flavonoid” means unsubstituted flavonoid or substitutedflavonoid (i.e. mono-substituted flavonoid, or/and di-substitutedflavonoid, or/and tri-substituted flavonoid). Examples of flavonoidsparticularly suitable for use in the present invention are one or moreflavones, one or more flavanones, one or more isoflavones, one or morecoumarins, one or more chromones, one or more dicoumarols, one or morechromanones, one or more chromanols, isomers (e.g., cis/trans isomers)thereof, and mixtures thereof.

Preferred for use herein are flavones and isoflavones, in particulardaidzein (7,4′-dihydroxy isoflavone), genistein (5,7,4′-trihydroxyisoflavone), equol (7,4′-dihydroxy isoflavan), 5,7-dihydroxy-4′-methoxyisoflavone, soy isoflavones (a mixture extracted from soy) and otherplant sources of such mixtures (e.g., red clover), and mixtures thereof.Also preferred are favanones such as hesperitin, hesperidin, andmixtures thereof.

Flavonoid compounds useful herein are commercially available from anumber of sources, e.g., Indofine Chemical Company, Inc., Steraloids,Inc., and Aldrich Chemical Company, Inc. Suitable flavonoids arecommercially available called Sterocare® offered by SEDERMA anddescribed in WO 99/18927.

In one embodiment, the herein described flavonoid compounds may be addedfrom about 0.01% to about 20%, more preferably from about 0.1% to about10%, and even more preferably from about 0.5% to about 5%, by weight ofthe composition.

9. N-acyl Amino Acid Compound

The topical compositions of the present invention can comprise one ormore N-acyl amino acid compounds. The amino acid can be one of any ofthe amino acids known in the art. The N-acyl amino acid compounds of thepresent invention can correspond to the formula:

wherein R can be a hydrogen, alkyl (substituted or unsubstituted,branched or straight chain), or a combination of alkyl and aromaticgroups.

Preferably, the N-acyl amino acid compound is selected from the groupcomprising N-acyl Phenylalanine, N-acyl Tyrosine, their isomers, theirsalts, and derivatives thereof. The amino acid can be the D or L isomeror a mixture thereof.

Among the broad class of N-acyl Phenylalanine derivatives, particularlyuseful is N-undecylenoyl-L-phenylalanine commercially available underthe tradename Sepiwhite® from SEPPIC.

In one embodiment, the present invention preferably comprises from about0.0001% to about 25%, more preferably from about 0.001% to about 10%,more preferably from about 0.01% to about 5%, and even more preferablyfrom about 0.02% to about 2.5% of the N-acyl amino acid by weight of thecomposition.

10. Retinoid

The compositions of this invention can comprise a retinoid, preferablyin a safe and effective amount such that the resultant composition issafe and effective for regulating keratinous tissue condition,preferably for regulating visible and/or tactile discontinuities inkeratinous tissue (e.g., regulating signs of skin aging). Thecompositions can comprise from about 0.001% to about 10%, morepreferably from about 0.005% to about 2%, even more preferably fromabout 0.01% to about 1%, still more preferably from about 0.01% to about0.5%, by weight of the composition, of the retinoid. The optimumconcentration used in a composition will depend on the specific retinoidselected since their potency can vary considerably.

As used herein, “retinoid” includes all natural and/or synthetic analogsof Vitamin A or retinol-like compounds which possess the biologicalactivity of Vitamin A in the skin as well as the geometric isomers andstereoisomers of these compounds. The retinoid is preferably selectedfrom retinol, retinol esters (e.g., C2-C22 alkyl esters of retinol,including retinyl palmitate, retinyl acetate, retinyl propionate),retinal, and/or retinoic acid (including all-trans retinoic acid and/or13-cis-retinoic acid), or mixtures thereof. More preferably the retinoidis a retinoid other than retinoic acid. These compounds are well knownin the art and are commercially available from a number of sources,e.g., Sigma Chemical Company, and Boerhinger Mannheim. Other retinoidswhich are useful herein are described in U.S. Pat. No. 4,677,120, U.S.Pat. No. 4,885,311, U.S. Pat. No. 5,049,584, U.S. Pat. No. 5,124,356,and Reissue 34,075. Other suitable retinoids can includetocopheryl-retinoate [tocopherol ester of retinoic acid (trans- orcis-), adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid},and tazarotene (ethyl642-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate). Preferredretinoids include retinol, retinyl palmitate, retinyl acetate, retinylpropionate, retinal and combinations thereof. More preferred is retinylpropionate, used most preferably from about 0.1% to about 0.3%.

The retinoid may be included as the substantially pure material, or asan extract obtained by suitable physical and/or chemical isolation fromnatural (e.g., plant) sources. The retinoid is preferably substantiallypure, more preferably essentially pure.

11. Optional Peptide

The composition of the present invention can comprise an additionalpeptide. Suitable peptides can include, but are not limited to, di-,tri-, tetra-, penta-, and hexa-peptides and derivatives thereof. In oneembodiment, the composition comprises from about 1×10−7% to about 20%,more preferably from about 1×10−6% to about 10%, even more preferablyfrom about 1×10−5% to about 5%, by weight of additional peptide.

As used herein, “additional peptide” refers to peptides containing tenor fewer amino acids and their derivatives, isomers, and complexes withother species such as metal ions (e.g., copper, zinc, manganese,magnesium, and the like). As used herein, peptide refers to bothnaturally occurring and synthesized peptides. Also useful herein arenaturally occurring and commercially available compositions that containpeptides.

Suitable additional dipeptides for use herein include but are notlimited to Carnosine (beta-Ala-His), Tyr-Arg, Val-Trp (WO 0164178),Asn-Phe, Asp-Phe. Suitable additional tripeptides for use hereininclude, but are not limited to Arg-Lys-Arg (Peptide CK), His-Gly-Gly.Gly-His-Lys, Gly-Gly-His, Gly-His-Gly, Lys-Phe-Lys. Suitable additionaltetrapeptides for use herein include but are not limited to, Peptide E,Arg-Ser-Arg-Lys (SEQ ID NO 44), Gly-Gln-Pro-Arg (SEQ ID NO 45). Suitableadditional pentapeptides include, but are not limited toLys-Thr-Thr-Lys-Ser (SEQ ID NO 43). Suitable hexapeptides include butare not limited to Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO 46) and such asthose disclosed in Fr 2854897 and Us 2004/0120918.

Other suitable additional peptides for use herein include, but are notlimited to lipophilic derivatives of peptides, preferably palmitoylderivatives, and metal complexes of the aforementioned (e.g., coppercomplex of the tripeptide His-Gly-Gly). Preferred additional dipeptidederivatives include N-Palmitoyl-beta-Ala-His,N-Acetyl-Tyr-Arg-hexadecylester (CALMOSENSINE™ from SEDERMA, France, WO9807744, U.S. Pat. No. 6,372,717). Preferred additional tripeptidederivatives include N-Palmitoyl-Gly-Lys-His, (Pal-GKH from SEDERMA,France, WO 0040611), a copper derivative of His-Gly-Gly soldcommercially as lamin, from Sigma, lipospondin (N-Elaidoyl-Lys-Phe-Lys)and its analogs of conservative substitution, N-Acetyl-Arg-Lys-Arg-NH2(Peptide CK+), N-Biot-Gly-His-Lys (N-Biot-GHK from SEDERMA, WO 0058347)and derivatives thereof. Suitable additional tetrapeptide derivativesfor use herein include, but are not limited toN-palmitoyl-Gly-Gln-Pro-Arg ((SEQ ID NO 50) from SEDERMA, France),suitable additional pentapeptide derivatives for use herein include, butare not limited to N-Palmitoyl-Lys-Thr-Thr-Lys-Ser ((SEQ ID NO 49)available as MATRIXYL™ from SEDERMA, France, WO 0015188 and U.S. Pat.No. 6,620,419) N-Palmitoyl-Tyr-Gly-Gly-Phe-X with X Met (SEQ ID NO 47)or Leu (SEQ ID NO 53) or mixtures thereof. Suitable additionalhexapeptide derivatives for use herein include, but are not limited toN-Palmitoyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ID NO 51) and derivativesthereof.

The preferred compositions commercially available containing aadditional tripeptide or a derivative include Biopeptide-CL™ by SEDERMA(WO 0143701), Maxilip™ by SEDERMA (WO 0143701), Biobustyl™ by SEDERMA.The compositions commercially available preferred sources of additionaltetrapeptides include RIGIN™ (WO 0043417), EYELISS™ (WO 03068141),MATRIXYL™, and MATRIXYL3000™ which contain between 50 and 500 ppm ofpalmitoyl-Gly-Gln-Pro-Arg (SEQ ID NO 50), and carrier, proposed bySEDERMA, France (Us 2004/0132667).

12. Ascorbates and Other Vitamins

The compositions of the present invention may comprise one or morevitamins, such as ascorbates (e.g., vitamin C, vitamin C derivatives,ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesiumascorbyl phosphate, sodium ascorbyl phosphate). Such vitamins caninclude, but are not limited to, vitamin B, vitamin B derivatives,vitamin B1 to vitamin B12 and theirs derivatives, vitamin K, vitamin Kderivatives, vitamin H vitamin D, vitamin D derivatives, vitamin E,vitamin E derivatives, and provitamins thereof, such as panthenol andmixtures thereof. The vitamin compounds may be included as thesubstantially pure material, or as an extract obtained by suitablephysical and/or chemical isolation from natural (e.g., plant) sources.In one embodiment, when vitamin compounds are present in thecompositions of the instant invention, the compositions comprise fromabout 0.0001% to about 50%, more preferably from about 0.001% to about10%, still more preferably from about 0.01% to about 8%, and still morepreferably from about 0.1% to about 5%, by weight of the composition, ofthe vitamin compound.

13. Particulate Material

The compositions of the present invention can comprise one or moreparticulate materials. Non limiting examples of particulate materialsuseful in the present invention include colored and uncolored pigments,interference pigments, inorganic powders, organic powders, compositepowders, optical brightener particles, and combinations thereof. Theseparticulates can, for instance, be platelet shaped, spherical, elongatedor needle-shaped, or irregularly shaped, surface coated or uncoated,porous or non-porous, charged or uncharged, and can be added to thecurrent compositions as a powder or as a pre-dispersion. In oneembodiment, particulate materials are present in the composition inlevels of from about 0.01% to about 20%, more preferably from about0.05% to about 10%, still more preferably from about 0.1% to about 5%,by weight of the composition. There are no specific limitations as tothe pigment, colorant or filler powders used in the composition.

Particulate materials useful herein can include, but are not limited to,bismuth oxychloride, sericite, silica, mica, mica treated with bariumsulfate or other materials, zeolite, kaolin, silica, boron nitride,lauroyl lysine, nylon, polyethylene, talc, styrene, polypropylene,polystyrene, ethylene/acrylic acid copolymer, aluminum oxide, siliconeresin, barium sulfate, calcium carbonate, cellulose acetate, PTFE,polymethyl methacrylate, starch, modified starches such as aluminumstarch octenyl succinate, silk, glass, and mixtures thereof. Preferredorganic powders/fillers include, but are not limited, to polymericparticles chosen from the methylsilsesquioxane resin microspheres suchas, for example, those sold by Toshiba silicone under the name Tospearl145A, microspheres of polymethylmethacrylates such as those sold bySeppic under the name Micropearl M 100, the spherical particles ofcrosslinked polydimethylsiloxanes, especially such as those sold by DowCorning Toray Silicone under the name Trefil E 506C or Trefil E 505C,spherical particles of polyamide and more specifically Nylon 12,especially such as those sold by Atochem under the name Orgasol 2002DNat C05, polystyrene microspheres such as for example those sold by DynoParticles under the name Dynospheres, ethylene acrylate copolymer soldby Kobo under the name FloBead EA209, PTFE, polypropylene, aluminiumstarch octenylsuccinate such as those sold by National Starch under thename Dry Flo, microspheres of polyethylene such as those sold byEquistar under the name of Microthene FN510-00, silicone resin,polymethylsilsesquioxane silicone polymer, platelet shaped powder madefrom L-lauroyl lysine, and mixtures thereof.

Also useful herein are interference pigments. The most common examplesof interference pigments are micas layered with about 50-300 nm films ofTiO2, Fe2O3, silica, tin oxide, and/or Cr2O3. Useful interferencepigments are available commercially from a wide variety of suppliers,for example, Rona (Timiron™ and Dichrona™), Presperse (Flonac™),Englehard (Duochrome™), Kobo (SK-45-R and SK-45-G), BASF (Sicopearls)and Eckart (e.g. Prestige Silk Red).

Other pigments useful in the present invention can provide colorprimarily through selective absorption of specific wavelengths ofvisible light, and include inorganic pigments, organic pigments andcombinations thereof. Examples of such useful inorganic pigments includeiron oxides, ferric ammonium ferrocyanide, manganese violet, ultramarineblue, and Chrome oxide. Organic pigments can include natural colorantsand synthetic monomeric and polymeric colorants. An example isphthalocyanine blue and green pigment. Also useful are lakes, primaryFD&C or D&C lakes and blends thereof. Also useful are encapsulatedsoluble or insoluble dyes and other colorants. Inorganic white oruncolored pigments useful in the present invention, for example TiO2,ZnO, or ZrO2, are commercially available from a number of sources. Oneexample of a suitable particulate material contains the materialavailable from U.S. Cosmetics (TRONOX TiO2 series, SAT-T CR837, a rutileTiO2), an other example is OPTISOL, proposed by Oxonica.

The pigments/powders of the current invention can be surface treated toprovide added stability of color and/or for ease of formulation.Non-limiting examples of suitable coating materials include silicones,lecithin, amino acids, metal soaps, polyethylene and collagen. Thesesurface treatments may be hydrophobic or hydrophilic, with hydrophobictreatments being preferred.

14. Sunscreen Actives

The compositions of the subject invention may optionally contain asunscreen active. As used herein, “sunscreen active” includes bothsunscreen agents and physical sunblocks. Suitable sunscreen actives maybe organic or inorganic.

A wide variety of conventional organic or inorganic sunscreen activesare suitable for use herein. In one embodiment, the compositioncomprises from about 0.1% to about 20%, more typically from about 0.5%to about 10% by weight of the composition, of the sun screen active.Exact amounts will vary depending upon the sunscreen chosen and thedesired Sun Protection Factor (SPF).

As examples of organic screening agents which are active in UV-A and/orUV-B, there may be mentioned in particular those designated below bytheir CTFA name:

-   -   para-aminobenzoic acid derivatives: PABA, Ethyl PABA, Ethyl        Dihydroxypropyl PABA, Ethylhexyl Dimethyl PABA sold in        particular under the name “ESCALOL 507” by ISP, Glyceryl PABA,        PEG-25 PABA sold under the name “UVINUL P25” by BASF,    -   salicyclic derivatives: Homosalate sold under the name “EUSOLEX        HMS” by RONA/EM INDUSTRIES, Ethylhexyl Salicylate sold under the        name “NEO HELIOPAN OS” by HAARMANN and REIMER, Dipropyleneglycol        Salicylate sold under the name “DIPSAL” by SCHER, TEA        Salicylate, sold under the name “NEO HELIOPAN TS” by HAARMANN        and REIMER,    -   dibenzoylmethane derivatives: Butyl Methoxydibenzoylmethane sold        in particular under the trademark “PARSOL 1789” by HOFFMANN LA        ROCHE, Isopropyl Dibenzolylmethane,    -   cinnamic derivatives: Ethylhexyl Methoxycinnamate sold in        particular under the trademark “PARSOL MCX” by HOFFMANN LA        ROCHE, Isopropyl Methoxy Cinnamate, Isoamyl Methoxy Cinnamate        sold under the trademark “NEO HELIOPAN E 1000” by HAARMANN and        REIMER, Cinoxate, DEA Methoxycinnamate, Diisopropyl        Methylcinnamate, Glyceryl Ethylhexanoate Dimethoxycinnamate,    -   ββ′-diphenylacrylate derivatives: Octocrylene sold in particular        under the trademark “UVINUL N539” by BASF, Etocrylene, sold in        particular under the trademark “UVINUL N35” by BASF,    -   benzophenone derivatives: Benzophenone-1 sold under the        trademark “UVINUL 400” by BASF, Benzophenone-2 sold under the        trademark “UVINUL D50” by BASF, Benzophenone-3 or Oxybenzone,        sold under the trademark “UVINUL M40” by BASF, Benzophenone-4        sold under the trademark “UVINUL MS40” by BASF, Benzophenone-5,        Benzophenone-6 sold under the trademark “HELISORB 11” by        NORQUAY, Benzophenone-8 sold under the trademark “SPECTRA-SORB        UV-24” by AMERICAN CYANAMID, Benzophenone-9 sold under the        trademark “UVINUL DS-49” by BASF, Benzophenone-12,    -   benzylidene camphor derivatives: 3-Benzylidene Camphor,        4-Methylbenzylidene Camphor sold under the name “EUSOLEX 6300”        by MERCK, Benzylidene Camphor Sulphonic Acid, Camphor        Benzalkonium Methosulphate, Terephthalylidene Dicamphor        Sulphonic Acid, Polyacrylamidomethyl Benzylidene Camphor,    -   phenylbenzimidazole derivatives: Phenylbenzimidazole Sulphonic        Acid sold in particular under the trademark “EUSOLEX 232” by        MERCK, Benzimidazilate sold under the trademark “NEO HELIOPAN        AP” by HAARMANN and REIMER,    -   triazine derivatives: Anisotriazine sold under the trademark        “TINOSORB S” by CIBA GEIGY, Ethylhexyl triazones sold in        particular under the trademark “UVINUL T150” by BASF,        Diethylhexyl Butamido Triazone sold under the trademark “UVASORB        HEB” by SIGMA 3V,    -   phenylbenzotriazole derivatives: Drometrizole Trisiloxane sold        under the name “SILATRIZOLE” by RHODIA CHIMIE,    -   anthranilic derivatives: Menthyl anthranilate sold under the        trademark “NEO HELIOPAN MA” by HAARMANN and REIMER,    -   imidazoline derivatives: Ethylhexyl Dimethoxybenzylidene        Dioxoimidazoline Propionate,    -   benzalmalonate derivatives: Polyorganosiloxane with        benzalmalonate functional groups sold under the trademark        “PARSOL SLX” by HOFFMANN LA ROCHE, and mixtures thereof.    -   others: dihydroxycinnamic acid derivatives (umbelliferone,        methylumbelliferone, methylaceto-umbelliferone);        trihydroxy-cinnamic acid derivatives (esculetin,        methylesculetin, daphnetin, and the glucosides, esculin and        daphnin); hydrocarbons (diphenylbutadiene, stilbene);        dibenzalacetone and benzalacetophenone; naphtholsulfonates        (sodium salts of 2-naphthol-3,6-disulfonic and of        2-naphthol-6,8-disulfonic acids); di-hydroxynaphthoic acid and        its salts; o- and p-hydroxybiphenyldisulfonates; coumarin        derivatives (7-hydroxy, 7-methyl, 3-phenyl); diazoles        (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl        naphthoxazole, various aryl benzothiazoles); quinine salts        (bisulfate, sulfate, chloride, oleate, and tannate); quinoline        derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); uric        and violuric acids; tannic acid and its derivatives (e.g.,        hexaethylether); (butyl carbotol) (6-propyl piperonyl)ether;        hydroquinone;

The organic UV-screening agents which are more particularly preferredare chosen from the following compounds: Ethylhexyl Salicylate, ButylMethoxydibenzoylmethane, Ethylhexyl Methoxycinnamate, Octocrylene,Phenylbenzimidazole Sulphonic Acid, Terephthalylidene DicamphorSulphonic, Benzophenone-3, Benzophenone-4, Benzophenone-5,4-Methylbenzylidene camphor, Benzimidazilate, Anisotriazine, Ethylhexyltriazone, Diethylhexyl Butamido Triazone, Methylene bis-BenzotriazolylTetramethylbutylphenol, Drometrizole Trisiloxane, and mixtures thereof.

Also preferred are the compositions described in U.S. Pat. No. 6,190,645and in particular, sunscreen agents sold under the trademarkINCROQUAT-UV-283 manufactured by Croda, Inc.

The inorganic screening agents which may be used in the compositionaccording to the invention are in particular nanopigments (mean size ofthe primary particles: generally between 5 nm and 100 nm, preferablybetween 10 nm and 50 nm) of coated or uncoated metal oxides such as forexample nanopigments of titanium oxide (amorphous or crystallized in theform of rutile and/or anatase), iron, zinc, zirconium or cerium oxidesand mixtures thereof. Coating agents are moreover alumina and/oraluminum stearate. Such nanopigments of metal oxides, coated oruncoated, are in particular described in EP-A-0-518,772 andEP-A-0-518,773. One preferred TiO2/ZnO2 sunscreen agent is OPTISOL,proposed by Oxonica

When used herein, the inorganic sunscreens are present in the amount offrom about 0.1% to about 20%, preferably from about 0.5% to about 10%,more preferably from about 1% to about 5%, by weight of the composition.

15. Anti-Cellulite Agents

The compositions of the present invention may also comprise ananti-cellulite agent. Suitable agents may include, but are not limitedto, xanthine compounds (e.g., caffeine, theophylline, theobromine, andaminophylline). In one embodiment, when anti-cellulite compounds arepresent in the compositions of the instant invention, the compositionscomprise from about 0.0001% to about 50%, more preferably from about0.001% to about 10%, still more preferably from about 0.01% to about 8%,and still more preferably from about 0.1% to about 5%, by weight of thecomposition, of the anti-cellulite compound. Especially useful arecombinations with the cellulite/slimming agents called Vexel™ (FR 2 654619), Coaxel (FR 2 694 195), Cyclolipase™ (FR 2 733 149), Pleurimincyl™and Lipocare™ (WO 98/43607), Redulite™ and Unislim™ (FR 0306063), alloffered by SEDERMA.

16. Slimming, Toning or Draining Actives

The compositions can include one or more lipolytic agent selected among:phosphodiesterase inhibitors (e.g., xanthine derivatives), alpha-2blockers compounds capable of blocking alpha-2 receptors at theadipocytes surface, beta-adrenergical agonists and antagonists (e.g.alverine and its organic or inorganic salts such as alverine citrate),agents inhibiting LDL and VLDL receptors synthesis, inhibitors ofenzymes of fatty acid synthesis such as acetylCoA carboxylase, or fattyacid synthetase or cerulenine, compounds stimulating beta receptorsand/or G proteins, glucose transport blockers such as serutine orrutine, neuropeptide Y (NPY) antagonists capable of blocking NPYreceptors at the adipocytes surface, cAMP and its cosmeticallyacceptable derivatives, adenylate cyclase enzyme active agents such asforskolin, agents modifying fat acids transport, lipolytic peptides andlipolytic proteins, like peptides or proteins such as the peptidesderived from the parathyroidal hormone, described in particular in thepatents FR 2788058 and FR 2781231.

Others examples of usable lipolytic agents include botanical and marineextracts:

-   -   among plant extracts, there may more particularly be mentioned        the extract of English ivy (Hedera Helix), of Chinese thorowax        (Bupleurum chinensis), of arnica (Arnica Montana L), of rosemary        (Rosmarinus officinalis N), of marigold (Calendula officinalis),        of sage (Salvia officinalis L), of ginseng (Panax ginseng), of        ginko biloba, of St.-John's-Wort (Hyperycum Perforatum), of        butcher's-broom (Ruscus aculeatus L), of European meadowsweet        (Filipendula ulmaria L), of big-flowered Jarva tea (Orthosiphon        Stamincus Benth), of algae (Fucus Vesiculosus), of birch (Betula        alba), of green tea, of cola nuts (Cola Nipida), of        horse-chestnut, of bamboo, of spadeleaf (Centella asiatica), of        heather, of fucus, of willow, of mouse-ear, extracts of escine,        extracts of cangzhu, extracts of chrysanthellum indicum,        extracts of the plants of the Armeniacea genus, Atractylodis        Platicodon, Sinnomenum, Pharbitidis, Flemingia, extracts of        Coleus such as C. Forskohlii, C. blumei, C. esquirolii, C.        scutellaroides, C. xanthantus and C. Barbatus, such as the        extract of root of Coleus barbatus, extracts of Ballote,        extracts of Guioa, of Davallia, of Terminalia, of Barringtonia,        of Trema, of antirobia, cecropia, argania, dioscoreae such as        Dioscorea opposita or Mexican,    -   as extracted of marine origin: extracts of algae or        phytoplankton such as an extract of Laminaria digitata, diatoms,        rhodysterol. All these extracts being able of course to be taken        in mixtures.

The compositions according to the invention can also contain in additionone or more additional active selected among: agents acting on themicrocirculation (vasculoprotectors or vasodilators) such as the naturalflavonoids, ruscogenines, esculosides, escine, nicotinates, heperidinemethyl chalcone, butcher's-broom, essential oils of lavender orrosemary, the extracts of Ammi visnaga; anti-glycation agents such asextracts of Centella asiatica and Siegesbeckia, silicium, amadorine,ergothioneine and its derivatives, hydroxystilbenes and theirderivatives (e.g. resveratrol), vegetable extracts of the family ofEricaceae, in particular bilberry extracts (Vaccinium angustifollium),vitamin C and its derivatives, retinol and its derivatives.

17. Butylated Hydroxytoluene (BHT) and Butylated Hydroxyanisole (BHA)

The topical compositions of the present invention may comprise BHT orBHA.

In one embodiment, BHT and/or BHA is added from about 0.0001% to about20% by weight of the composition, more preferably from about 0.001% toabout 10%, even more preferably from about 0.01% to about 5%, and stillmore preferably from about 0.1% to about 0.5%.

18. Topical Anesthetics

The compositions of the present invention may also contain a safe andeffective amount of a topical anesthetic. Examples of topical anestheticdrugs include benzocaine, lidocaine, bupivacaine, chlorprocaine,dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine,procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceuticallyacceptable salts thereof.

19. Desquamating/Keratolytic Actives

A desquamating/keratolytic active may be added to the compositions ofthe present invention. In one embodiment, the composition comprises fromabout 0.01% to about 10%, preferably from about 0.1% to about 5%, morepreferably from about 0.5% to about 2%, by weight of the composition, ofa desquamating/keratolytic active.

Examples of useful keratolytic and/or desquamating agents include urea,salicylic acid and alkyl derivatives thereof, saturated and unsaturatedmonocarboxylic acids, saturated and unsaturated bicarboxylic acids,tricarboxylic acids, alpha hydroxyacids and beta hydroxyacids ofmonocarboxylic acids, alpha hydroxyacids and beta hydroxyacids ofbicarboxylic acids, alpha hydroxyacids and beta hydroxyacids oftricarboxylic acids, ketoacids, alpha ketoacids, beta ketoacids, of thepolycarboxylic acids, of the polyhydroxy monocarboxylic acids, of thepolyhydroxy bicarboxylic acids, of the polyhydroxy tricarboxylic acids.

Illustrative of this group of materials are 2-hydroxyethanoic acid(glycolic acid); 2-hydroxypropanoic acid (lactic acid); 2-methyl2-hydroxypropanoic acid (methyllactic acid); 2-hydroxybutanoic acid;2-hydroxypentanoic acid; 2-hydroxyhexanoic acid; 2-hydroxyheptanoicacid; 2-hydroxyoctanoic acid; 2hydroxynonanoic acid; 2-hydroxydecanoicacid; 2-hydroxyundecanoic acid; 2-hydroxydodecanoic acid(alpha-hydroxylauric acid); 2-hydroxytetradecanoic acid(alpha-hydroxymyristic acid); 2-hydroxyhexadecanoic acid(alpha-hydroxypalmitic acid); 2-hydroxyoctadecanoic acid(alpha-hydroxystearic acid); 2-hydroxyeicosanoic acid(alpha-hydroxyarachidonic acid); 2-phenyl 2-hydroxyethanoic acid(mandelic acid); 2,2-diphenyl 2-hydroxyethanoic acid (benzilic acid);3-phenyl 2-hydroxypropanoic acid (phenyl lactic acid); 2-phenyl 2-methyl2-hydroxyethanoic acid (atrolactic acid); 2-(4′-hydroxyphenyl)2-hydroxyethanoic acid; 2-(4′-chlorophenyl 2-hydroxyethanoic acid;2-(3′-hydroxy-4′-methoxyphenyl) 2-hydroxyethanoic acid;2-(4′-hydroxy-3′-methoxyphenyl) 2-hydroxyethanoic acid;3′-(2-hydroxyphenyl) 2-hydroxypropanoic acid; 3-(4′-hydroxyphenyl)2-hydroxypropanoic acid; and 2-(3′,4′dihydroxyphenyl), and2-hydroxyethanoic acid, 5-n-octanoylsalicylic acid,5-n-dodecanoylsalicylic acid, 5-n-decanoylsalicylic acid,5-n-octylsalicylic acid, 5-n-heptyloxysalicylic acid,4-n-heptyloxysalicylic acid and 2-hydroxy-3-methylbenzoic acid or alkoxyderivatives thereof, such as 2-hydroxy-3-methyoxybenzoic acid.

Preferred keratolytic agents are selected from the group comprisingglycolic acid, tartaric acid, salicylic acid, citric acid, lactic acid,pyruvic acid, gluconic acid, glucuronic acid, malic acid, mandelic acid,oxalic acid, malonic acid, succinic acid, acetic acid, phenol,resorcine, retinoic acid, adapalene, trichloroacetic acid, 5-fluorouracil, azelaic acid. Keratolytic agents are also the salts, esters,possible cis or trans forms, racemic mixtures and/or the relativedextrorotatory or levorotatory forms of the above listed compounds. Suchsubstances can be used singularly or in associations with each other.

Other keratolytic agents suitable for use herein can include enzymaticexfoliant based on a protease called Keratoline™ and offered by Sederma.

One desquamation system that is suitable for use herein comprisessalicylic acid and zwitterionic surfactants and is described in U.S.Pat. No. 5,652,228. Another desquamation system that is suitable for useherein contains sulfhydryl compounds and zwitterionic surfactants and isdescribed in U.S. Pat. No. 5,681,852. Zwitterionic surfactants such asthose described in this referenced patent can also be useful asdesquamatory agents herein, with cetyl betaine being particularlypreferred.

20. Anti-Acne Actives

The compositions of the present invention can comprise one or moreanti-acne actives. Examples of useful anti-acne actives includeresorcinol, sulfur, erythromycin, salicylic acid, benzoyl peroxide,dehydroacetic acid and zinc. Further examples of suitable anti-acneactives are described in U.S. Pat. No. 5,607,980. Especially useful arecombinations with the anti-acne ingredient called Ac.Net™ offered bySEDERMA (WO 03/028692 A2).

In one embodiment, when anti-acne compounds are present in thecompositions of the instant invention, the compositions comprise fromabout 0.0001% to about 50%, more preferably from about 0.001% to about10%, still more preferably from about 0.01% to about 8%, and still morepreferably from about 0.1% to about 5%, by weight of the composition, ofthe anti-acne compound.

21. Anti-Wrinkle Actives/Anti-Atrophy Actives

The compositions of the present invention can comprise a one or moreanti-wrinkle actives or anti-atrophy actives. Exemplaryanti-wrinkle/anti-atrophy actives suitable for use in the compositionsof the present invention include sulfur-containing D and L amino acidsand their derivatives and salts, particularly the N-acetyl derivatives,a preferred example of which is N-acetyl-L-cysteine; thiols, e.g. ethanethiol, hydroxy acids (e.g., alpha-hydroxy acids such as lactic acid andglycolic acid or beta-hydroxy acids such as salicylic acid and salicylicacid derivatives such as the octanoyl derivative, lactobionic acid),keto acids (e.g., pyruvic acid), phytic acid, ascorbic acid (vitamin C),stilbenes, cinnamates, resveratrol, kinetin, zeatin,dimethylaminoethanol, peptides from natural sources (e.g., soypeptides), and salts of sugar acids (e.g., Mn gluconate, Zn gluconate),lipoic acid; lysophosphatidic acid, skin peel agents (e.g., phenol andthe like), vitamin B3 compounds and retinoids and other vitamin Bcompounds (e.g., thiamine (vitamin B1), pantothenic acid (vitamin B5),riboflavin (vitamin B2), and their derivatives and salts (e.g., HCLsalts or calcium salts). Especially useful are combinations with thewrinkle agents called Dermolectine™ and Sterocare™ offered by SEDERMA(WO99/18927).

In one embodiment, when anti-wrinkle/anti-atrophy compounds are presentin the compositions of the instant invention, the compositions comprisefrom about 0.0001% to about 50%, more preferably from about 0.001% toabout 10%, still more preferably from about 0.01% to about 8%, and stillmore preferably from about 0.1% to about 5%, by weight of thecomposition, of the anti-wrinkle/anti-atrophy compound.

22. Anti-Oxidants/Racial Scavengers

The compositions of the present invention can include ananti-oxidant/radical scavenger. In one embodiment, the compositioncomprises from about 0.01% to about 10%, more preferably from about 0.1%to about 5%, of an anti-oxidant/radical scavenger.

Anti-oxidants/radical scavengers such as retinyl palmitate, ascorbicacid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbicacid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbylphosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherolsorbate, tocopherol acetate, other esters of tocopherol, butylatedhydroxy benzoic acids and their salts, peroxides including hydrogenperoxide, perborate, thioglycolates, persulfate salts,6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commerciallyavailable under the tradename Trolox®), gallic acid and its alkylesters, especially propyl gallate, uric acid and its salts and alkylesters, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine),nordihydroguaiaretic acid, bioflavonoids, sulfhydryl compounds (e.g.,glutathione), dihydroxy fumaric acid and its salts, lysine pidolate,arginine pilolate, amino acids, silymarin, lysine, 1-methionine,proline, superoxide dismutase, sorbic acids and its salts, lipoic acid,olive extracts, tea extracts, polyphenols such as proanthocyanidine frompine bark, carotenoids, curcumin compounds such as tetrahydrocurcumin,OCTA (L-2-oxo-4-thiazolidine carboxylic acid), glutathione, melanin,rosemary extracts and grape skin/seed extracts may be used. Preferredanti-oxidants/radical scavengers can be selected from esters oftocopherol, more preferably tocopherol acetate and tocopherol sorbate(U.S. Pat. No. 4,847,071)

23. Humectants, Moisturizers and Conditioning Agents

The compositions of the present invention can contain a safe andeffective amount of a conditioning agent selected from, for example,humectants, moisturizers, and skin conditioners. A variety of thesematerials can be employed and in one embodiment can be present at alevel of from about 0.01% to about 20%, more preferably from about 0.1%to about 10%, and still more preferably from about 0.5% to about 7%, byweight of the composition. These materials can include, but are notlimited to, guanidine, urea, glycolic acid, glycolate salts (e.g.ammonium and quaternary alkyl ammonium), salicylic acid, lactic acid,lactate salts (e.g., ammonium and quaternary alkyl ammonium), aloe verain any of its variety of forms (e.g., aloe vera gel), polyhydroxyalcohols such as sorbitol, mannitol, xylitol, erythritol, glycerol,hexanetriol, butanetriol, propylene glycol, butylene glycol, hexyleneglycol and the like, polyethylene glycols, sugars (e.g., melibiose),starches, sugar and starch derivatives (e.g., alkoxylated glucose,fructose, glucosamine), hyaluronic acid, lactamide monoethanolamine,acetamide monoethanolamine, panthenol, allantoin, petroleum and mixturesthereof. Also useful herein are the propoxylated glycerols described inU.S. Pat. No. 4,976,953.

Also useful are various C1-C30 monoesters and polyesters of sugars andrelated materials. These esters are derived from a sugar or polyolmoiety and one or more carboxylic acid moieties.

Preferably, the conditioning agent is selected from urea, guanidine,sucrose polyester, panthenol, dexpanthenol, allantoin, glycerol, andcombinations thereof.

Humectants can be selected from the group consisting of polyhydricalcohols, water soluble alkoxylated nonionic polymers, and mixturesthereof. Polyhydric alcohols useful herein include polyhydroxy alcoholsaforementioned and glycerin, hexylene glycol, ethoxylated glucose,1,2-hexane diol, dipropylene glycol, trehalose, diglycerin, maltitol,maltose, glucose, fructose, sodium chondroitin sulfate, sodiumhyaluronate, sodium adenosine phosphate, sodium lactate, pyrrolidonecarbonate, glucosamine, cyclodextrin, and mixtures thereof. Watersoluble alkoxylated nonionic polymers useful herein include polyethyleneglycols and polypropylene glycols having a molecular weight of up toabout 1000 such as those with CTFA names PEG-200, PEG-400, PEG-600,PEG-1000, PPG-12/SMDI copolymer and mixtures thereof.

24. Active Oxygen Generation Inhibitors

The compositions of the present invention may also comprise a an activeoxygen generation inhibitor selected from the group comprisingquercetin, rutin, taxifolin, kaempferol, myricetin, curcumin,resveratrol, arecoline, apigenin, wogonin, luteolin, tectorigenin, and amixture thereof.

This active oxygen generation inhibitor may be contained in an amount ofabout 0.001% to about 5%, more preferably in an amount of about 0.01% toabout 3% %, by weight of the composition.

25. Chelators

The compositions of the present invention may also comprise a chelatoror chelating agent. As used herein, “chelator” or “chelating agent”means an active agent capable of removing a metal ion from a system byforming a complex so that the metal ion cannot readily participate in orcatalyze oxygen radical formation. In one embodiment, a chelating agentis added to a composition of the present invention, preferably fromabout 0.00001% to about 10%, more preferably from about 0.001% to about5%, by weight of the composition. Exemplary chelators that are usefulherein include those that are disclosed in U.S. Pat. No. 5,487,884, WO91/16035 and WO 91/16034. Examples of chelating agents includeN-hydroxysuccinimide, EDTA, Disodium EDTA, NTA, deferoxamine, hydroxamicacids and their salts, phytic acid, phytate, gluconic acid and itssalts, transferrine, lactoferrin; furildioxime and derivatives thereof.

26. Anti-Inflammatory Agents

An anti-inflammatory agent may be added to the compositions of thepresent invention. In one embodiment, an anti-inflammatory agent isadded at a level of from about 0.01% to about 10%, preferably from about0.5% to about 5%, by weight of the composition. The exact amount ofanti-inflammatory agent to be used in the compositions will depend onthe particular anti-inflammatory agent utilized since such agents varywidely in potency Steroidal anti-inflammatory agents can include, butare not limited to, corticosteroids such as hydrocortisone. In addition,nonsteroidal anti-inflammatory agents can be useful herein. Thevarieties of compounds encompassed by this group are well known to thoseskilled in the art. Specific non-steroidal anti-inflammatory agents thatcan be useful in the composition of the present invention include, butare not limited to, oxicams such as piroxicam, salicylates such asaspirin; acetic acid derivatives, such as felbinac, fenamates, such asetofenamate, flufenamic, mefenamic, meclofenamic, acids; propionic acidderivatives, such as ibuprofen, naproxen, pyrazoles, and mixturesthereof. Mixtures of these non-steroidal anti-inflammatory agents mayalso be employed, as well as the dermatologically acceptable salts andesters of these agents.

Finally, so-called “natural” anti-inflammatory agents are useful inmethods of the present invention. Such agents may suitably be obtainedas an extract by suitable physical and/or chemical isolation fromnatural sources (e.g., plants, fungi, by-products of microorganisms) orcan be synthetically prepared. For example, candelilla wax, bisabolol(e.g., alpha bisabolol), aloe vera, plant sterols (e.g., phytosterol),Manjistha (extracted from plants in the genus Rubia, particularly RubiaCordifolia), and Guggal (extracted from plants in the genus Commiphora,particularly Commiphora Mukul), kola extract, chamomile, red cloverextract, Piper methysticum extract (Kava Kava from SEDERMA (FR 2 771 002and WO 99/25369), Bacopa monieri extract (Bacocalmine™ from SEDERMA, WO99/40897) and sea whip extract, may be used. Anti-inflammatory agentsuseful herein include allantoin and compounds of the Licorice (the plantgenus/species Glycyrrhiza glabra) family, including glycyrrhetic acid,glycyrrhizic acid, and derivatives thereof (e.g., salts and esters).Suitable salts of the foregoing compounds include metal and ammoniumsalts. Suitable esters include C2-C24 saturated or unsaturated esters ofthe acids, preferably C10-C24, more preferably C16-C24. Specificexamples of the foregoing include oil soluble licorice extract, theglycyrrhizic and glycyrrhetic acids themselves, monoammoniumglycyrrhizinate, monopotassium glycyrrhizinate, dipotassiumglycyrrhizinate, 1-beta-glycyrrhetic acid, stearyl glycyrrhetinate, and3-stearyloxy-glycyrrhetinic acid, and disodium3-succinyloxy-beta-glycyrrhetinate. Stearyl glycyrrhetinate ispreferred. Additional anti inflammatory agents include diosgenol,saponines, sapogenines, lignanes, triterpenes saponosides and genines.

27. Tanning Actives

The compositions of the present invention can comprise a tanning active.In one embodiment, the composition comprises from about 0.1% to about20%, more preferably from about 2% to about 7%, and even more preferablyfrom about 3% to about 6%, by weight of the composition, of a tanningactive. A preferred tanning active is dihydroxyacetone, which is alsoknown as DHA or 1,3-dihydroxy-2-propanone. Especially useful arecombinations with the tanning agents called Tyr-Ol™ and Tyr-Excel™offered by SEDERMA and described in Fr 2 702 766 and WO 03/017966respectively.

28. Skin Lightening Agents

The compositions of the present invention may contain a skin lighteningagent. When used, the compositions preferably contain from about 0.001%to about 10%, more preferably from about 0.02% to about 5%, alsopreferably from about 0.05% to about 2%, by weight of the composition,of a skin lightening agent. Suitable skin lightening agents includethose known in the art, including kojic acid, hydroquinone, aminophenolderivatives, N-cholesteryloxycarbonyl-para-aminophenol andN-ethyloxycarbonyl-para-aminophenol; iminophenol derivatives,L-2-oxothiazolidine-4-carboxylic acid or procysteine, and also its saltsand esters, arbutin, tranexamic acid, ascorbic acid and derivativesthereof (e.g., magnesium ascorbyl phosphate or sodium ascorbylphosphate, ascorbyl glucoside and the like (such as AA2G fromHayashibara)), and extracts (e.g., mulberry extract, placental extract,skullcap extract broussonetia extract, oil soluble liquorice extract(such as these available from Maruzen), oil soluble liquorice extract(glycyrrhiza, chamomile extract (such as these available from Kao)),m-Tranexamic acid/vitamin C ethyl (such as these available fromShiseido), adenosine monophosphate disodium (APM offered by Otsuka),ellagic acid (Lion), rucinol (Pola), ethyl ascorbyl ether). Skinlightening agents suitable for use herein also include those describedin WO95/34280, PCT/US 95/07432, co-pending. U.S. Ser. No. 08/390,152 andPCT/US 95/23780. Especially useful are combinations with the skinlightening agents called Melaclear™, Etioline™, Melaslow™ and Lumiskin™offered by SEDERMA and described respectively in FR 2 732 215, WO98/05299, WO 02/15871 and PCT/FR 03/02400. Other skin lighteningmaterials suitable for use herein can include Actiwhite® (Cognis),Emblica® (Rona), Azeloglicina (Sinerga) and Sepiwhite® (Seppic). Apreferred skin lightening agent is ascorbyl glucoside.

29. Antimicrobial, Antibacterial and Antifungal Actives

The compositions of the present invention can comprise one or moreanti-fungal or anti-microbial actives. A safe and effective amount of anantimicrobial or antifungal active can be added to the presentcompositions. In one embodiment, the composition comprises from about0.001% to about 10%, preferably from about 0.01% to about 5%, and morepreferably from about 0.05% to about 2%, by weight of the composition,of an antimicrobial or antifungal active.

Suitable anti-microbial actives include coal tar, sulfur, whitfield'sointment, castellani's paint, aluminum chloride, gentian violet,octopirox (piroctone olamine), 3,4,4′-trichlorocarbanilide (trichlosan),triclocarban, ciclopirox olamine, undecylenic acid and it's metal salts,potassium permanganate, selenium sulphide, sodium thiosulfate, propyleneglycol, oil of bitter orange, urea preparations, griseofulvin,8-Hydroxyquinoline ciloquinol, thiobendazole, thiocarbamates,haloprogin, polyenes, hydroxypyridone, morpholine, benzylamine,allylamines (such as terbinafine), tea tree oil, clove leaf oil,coriander, palmarosa, berberine, thyme red, cinnamon oil, cinnamicaldehyde, citronellic acid, hinokitol, ichthyol pale, Sensiva SC-50,Elestab HP-100, azelaic acid, lyticase, iodopropynyl butylcarbamate(IPBC), isothiazalinones such as octyl isothiazolinbne and azoles, andcombinations thereof. Preferred anti-microbials include itraconazole,ketoconazole, selenium sulphide and coal tar. In one embodiment, one ormore anti-fungal or anti-microbial active is combined with ananti-dandruff active selected from polyvalent metal salts of pyrithione.

a. Azoles

Azole anti-microbials include imidazoles such as benzimidazole,benzothiazole, bifonazole, butoconazole nitrate, climbazole,clotrimazole, croconazole, eberconazole, econazole, elubiol,fenticonazole, fluconazole, flutimazole, isoconazole, ketoconazole,lanoconazole, metronidazole, miconazole, neticonazole, omoconazole,oxiconazole nitrate, sertaconazole, sulconazole nitrate, tioconazole,thiazole, and triazoles such as terconazole and itraconazole, andcombinations thereof. When present in the composition, the azoleanti-microbial active is included in an amount from about 0.01% to about5%, preferably from about 0.1% to about 3%, and more preferably fromabout 0.3% to about 2%, by weight of the composition. Especiallypreferred herein are ketoconazole and climbazole.

b. Selenium Sulfide

Selenium sulfide is a particulate anti-dandruff agent suitable for usein the anti-microbial compositions of the present invention, effectiveconcentrations of which range from about 0.1% to about 4%, by weight ofthe composition, preferably from about 0.3% to about 2.5%, morepreferably from about 0.5% to about 1.5

c. Sulfur

Sulfur may also be used as a particulate anti-microbial/anti-dandruffagent in the anti-microbial compositions of the present invention.Effective concentrations of the particulate sulfur are typically fromabout 1% to about 4%, by weight of the composition, preferably fromabout 2% to about 4%.

d. Additional Anti-Microbial Actives

Additional anti-microbial actives of the present invention may includeone or more keratolytic agents such as salicylic acid, extracts ofmelaleuca (tea tree) and charcoal. The present invention may alsocomprise combinations of anti-microbial actives. Such combinations mayinclude octopirox and zinc pyrithione combinations, pine tar and sulfurcombinations, salicylic acid and zinc pyrithione combinations, octopiroxand climbasole combinations, and salicylic acid and octopiroxcombinations, and mixtures thereof.

Preferred examples of actives useful herein include those selected fromthe group consisting of benzoyl peroxide, 3-hydroxy benzoic acid,glycolic acid, lactic acid, 4-hydroxy benzoic acid, 2-hydroxybutanoicacid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, phytic acid,lipoic acid, azelaic acid, arachidonic acid, benzoylperoxide,tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen,resorcinol, phenoxyethanol, phenoxypropanol, phenoxyisopropanol,2,4,4′-trichloro-2′-hydroxy diphenyl ether, 3,4,4′-trichlorocarbanilide,octopirox, ciclopirox, lidocaine hydrochloride, clotrimazole,miconazole, ketoconazole, neomycin sulfate, and mixtures thereof.

Especially useful are combinations with the ingredient range calledOSMOCIDE™ offered by SEDERMA (WO 97/05856).

30. Thickening Agents (Including Thickeners and Gelling Agents)

The compositions of the present invention can comprise one or morethickening agents. In one embodiment, a thickening agent is present at alevel of from about 0.05% to about 10%, preferably from about 0.1% toabout 5%, and more preferably from about 0.25% to about 4%, by weight ofthe composition. Nonlimiting classes of thickening agents include thoseselected from the following:

a. Carboxylic Acid Polymers

These polymers are crosslinked compounds containing one or more monomersderived from acrylic acid, substituted acrylic acids, and salts andesters of these acrylic acids and the substituted acrylic acids, whereinthe crosslinking agent contains two or more carbon-carbon double bondsand is derived from a polyhydric alcohol. Polymers useful in the presentinvention are more fully described in U.S. Pat. No. 5,087,445, U.S. Pat.No. 4,509,949, U.S. Pat. No. 2,798,053, and in CTFA InternationalCosmetic Ingredient Dictionary, Tenth Edition, 2004.

Examples of commercially available carboxylic acid polymers usefulherein include the carbomers, which are homopolymers of acrylic acidcrosslinked with allyl ethers of sucrose or pentaerytritol. Thecarbomers are available as the Carbopol® 900 series from B.F. Goodrich(e.g., Carbopol® 954). In addition, other suitable carboxylic acidpolymeric agents include Ultrez® 10 (B.F. Goodrich) and copolymers ofC10-30 alkyl acrylates with one or more monomers of acrylic acid,methacrylic acid, or one of their short chain (i.e., C1-4 alcohol)esters, wherein the crosslinking agent is an allyl ether of sucrose orpentaerytritol. These copolymers are known as acrylates/C10-C30 alkylacrylate crosspolymers and are commercially available as Carbopol® 1342,Carbopol® 1382, Pemulen TR-1, and Pemulen TR-2, from B.F. Goodrich. Inother words, examples of carboxylic acid polymer thickeners usefulherein are those selected from carbomers, acrylates/C10-C30 alkylacrylate crosspolymers, and mixtures thereof

b. Crosslinked Polyacrylate Polymers

The compositions of the present invention can optionally containcrosslinked polyacrylate polymers useful as thickeners or gelling agentsincluding both cationic and nonionic polymers, with the cationics beinggenerally preferred. Examples of useful crosslinked nonionicpolyacrylate polymers and crosslinked cationic polyacrylate polymers arethose described in U.S. Pat. No. 5,100,660, U.S. Pat. No. 4,849,484,U.S. Pat. No. 4,835,206, U.S. Pat. No. 4,628,078 U.S. Pat. No. 4,599,379and EP 228,868.

c. Polyacrylamide Polymers

The compositions of the present invention can optionally containpolyacrylamide polymers, especially nonionic polyacrylamide polymersincluding substituted branched or unbranched polymers. Preferred amongthese polyacrylamide polymers is the nonionic polymer given the CTFAdesignation polyacrylamide and isoparaffin and laureth-7, availableunder the Tradename Sepigel 305 from Seppic Corporation.

Other polyacrylamide polymers useful herein include multi-blockcopolymers of acrylamides and substituted acrylamides with acrylic acidsand substituted acrylic acids. Commercially available examples of thesemulti-block copolymers include Hypan SR150H, SS500V, SS500W, SSSA100H,from Lipo Chemicals, Inc.

The compositions may also contain thickening and texturising gels of thetype as exemplified by the product range called Lubrajel® from UnitedGuardian. These gels have moisturizing, viscosifying, stabilizingproperties and may be used in concentration ranges between 1 and 99%,most advantageously between 5 and 15%.

d. Polysaccharides

A wide variety of polysaccharides can be useful herein.“Polysaccharides” refer to gelling agents that contain a backbone ofrepeating sugar (i.e., carbohydrate) units. Nonlimiting examples ofpolysaccharide gelling agents include those selected from the groupconsisting of cellulose, carboxymethyl hydroxyethylcellulose, celluloseacetate propionate carboxylate, hydroxyethylcellulose, hydroxyethylethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose,methyl hydroxyethylcellulose, microcrystalline cellulose, sodiumcellulose sulfate, and mixtures thereof. Also useful herein are thealkyl-substituted celluloses. Preferred among the alkyl hydroxyalkylcellulose ethers is the material given the CTFA designation cetylhydroxyethylcellulose, which is the ether of cetyl alcohol andhydroxyethylcellulose. This material is sold under the tradenameNatrosol® CS Plus from Aqualon Corporation.

Other useful polysaccharides include scleroglucans comprising a linearchain of (1-3) linked glucose units with a (1-6) linked glucose everythree units, a commercially available example of which is Clearogel™CS11 from Michel Mercier Products Inc.

e. Gums

Other thickening and gelling agents useful herein include materialswhich are primarily derived from natural sources. Nonlimiting examplesof these gelling agent gums include acacia, agar, algin, alginic acid,ammonium alginate, amylopectin, calcium alginate, calcium carrageenan,carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guarhydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydratedsilica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp,locust bean gum, natto gum, potassium alginate, potassium carrageenan,propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextran,sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

31. Antiperspirant Actives

Antiperspirant actives may also be included in the compositions of thepresent invention. Suitable antiperspirant actives include astringentmetallic salts, especially the inorganic and organic salts of aluminumzirconium and zinc, as well as mixtures thereof. Particularly preferredare the aluminum containing and/or zirconium-containing materials orsalts, such as aluminum halides, aluminum chlorohydrate, aluminumhydroxyhalides, zirconyl oxyhalides, zirconyl hydroxyhalides, andmixtures thereof. In one embodiment, when antiperspirant actives arepresent in the compositions of the instant invention, the compositionscomprise from about 0.01% to about 50%, more preferably from about 0.1%to about 40%, and still more preferably from about 1% to about 30%, byweight of the composition, of the antiperspirant compound.

32. Detersive Surfactants

The compositions of the present invention can include detersivesurfactant from about 1% to about 90%, more preferably from about 5% toabout 10%. The detersive surfactant component can be included to providecleaning performance to the composition. The detersive surfactantcomponent in turn can comprise anionic detersive surfactant,zwitterionic or amphoteric detersive surfactant, or a combinationthereof. Suitable anionic detersive surfactant components for use in thecomposition herein include those which are known for use in hair care orother personal care cleansing compositions. When included, theconcentration of the anionic surfactant component in the composition canpreferably be sufficient to provide the desired cleaning and latherperformance, and generally can range from about 5% to about 50%,preferably from about 8% to about 30%, more preferably from about 10% toabout 25%, even more preferably from about 12% to about 22%.

Preferred anionic surfactants suitable for use in the compositions arethe alkyl and alkyl ether sulfates. Other suitable anionic detersivesurfactants are the water-soluble salts of organic, sulfuric acidreaction products, alkoyl isethionates, sodium or potassium salts offatty acid amides of methyl tauride, olefin sulfonates, andbeta-alkyloxy alkane sulfonates. Preferred anionic detersive surfactantsfor use in the compositions include ammonium lauryl sulfate, ammoniumlaureth sulfate, triethylamine lauryl sulfate, triethylamine laurethsulfate, triethanolamine lauryl sulfate, triethanolamine laurethsulfate, monoethanolamine lauryl sulfate, monoethanolamine laurethsulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate,lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodiumlaureth sulfate, potassium lauryl sulfate, potassium laureth sulfate,sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine,cocoyl sarcosine, ammonium cocoyl sulfate, ammonium lauroyl sulfate,sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate,potassium lauryl sulfate, triethanolamine lauryl sulfate,triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate,monoethanolamine lauryl sulfate, sodium tridecyl benzene sulfonate,sodium dodecyl benzene sulfonate, sodium cocoyl isethionate andcombinations thereof.

Suitable amphoteric or zwitterionic detersive surfactants for use in thecomposition herein include those which are known for use in hair care orother personal care cleansing. Concentration of such amphotericdetersive surfactants preferably ranges from about 0.5% to about 20%,preferably from about 1% to about 10%. Non limiting examples of suitablezwitterionic or amphoteric surfactants are described in U.S. Pat. Nos.5,104,646 and 5,106,609.

Amphoteric detersive surfactants include derivatives of aliphaticsecondary and tertiary amines.

The compositions of the present invention may further compriseadditional surfactants for use in combination with the anionic detersivesurfactant component described hereinbefore. Suitable optionalsurfactants include nonionic and cationic surfactants. Any suchsurfactant known in the art for use in hair or personal care productsmay be used, provided that the optional additional surfactant is alsochemically and physically compatible with the essential components ofthe composition, or does not otherwise unduly impair productperformance, aesthetics or stability. The concentration of the optionaladditional surfactants in the composition may vary with the cleansing orlather performance desired, the optional surfactant selected, thedesired product concentration, the presence of other components in thecomposition, and other factors well known in the art.

Non limiting examples of other anionic, zwitterionic, amphoteric oroptional additional surfactants suitable for use in the compositions aredescribed in McCutcheon's, Emulsifiers and Detergents, 1989 Annual,published by M.C. Publishing Co., and U.S. Pat. Nos. 3,929,678,2,658,072; 2,438,091; 2,528,378.

33. Cationic, Anionic and Amphoteric Polymers

The compositions of the present invention can comprise polymers whichmay be homopolymers, copolymers, terpolymers, etc. For convenience indescribing the polymers hereof, monomeric units present in the polymersmay be referred to as the monomers from which they can be derived. Themonomers can be ionic (e.g., anionic, cationic, amphoteric,zwitterionic) or non-ionic.

When included, concentrations of the cationic polymer in the compositioncan typically range from about 0.05% to about 3%, preferably from about0.075% to about 2.0%, more preferably from about 0.1% to about 1.0

a. Cationic Polymers

Suitable cationic polymers for use in the compositions of the presentinvention contain cationic nitrogen-containing moieties such asquaternary ammonium or cationic protonated amino moieties. Any anioniccounterions can be used in association with the cationic polymers solong as the polymers remain soluble in water, in the composition, or ina coacervate phase of the composition, and so long as the counterionsare physically and chemically compatible with the essential componentsof the composition or do not otherwise unduly impair productperformance, stability or aesthetics. Non limiting examples of suchcounterions include halides (e.g., chloride, fluoride, bromide, iodide),sulfate and methylsulfate. Non limiting examples of such polymers aredescribed in the CTFA.

Non limiting examples of suitable cationic polymers include copolymersof vinyl monomers having cationic protonated amine or quaternaryammonium functionalities with water soluble spacer monomers such asacrylamide, methacrylamide, alkyl and dialkyl acrylamides, alkyl anddialkyl methacrylamides, alkyl acrylate, alkyl methacrylate, vinylcaprolactone or vinyl pyrrolidone.

Examples of cationic monomers include monomers derived from acrylic acidor methacrylic acid, and a quaternarized epihalohydrin product of atrialkylamine having 1 to 5 carbon atoms in the alkyl such as(meth)acryloxypropyltrimethylammonium chloride and(meth)acryloxypropyltriethylammonium bromide; amine derivatives ofmethacrylic acid or amine derivatives of methacrylamide derived frommethacrylic acid or methacrylamide and a dialkylalkanolamine havingC1-C6 alkyl groups such as dimethylaminoethyl (meth)acrylate,diethylaminoethyl (meth)acrylate, dimethylaminopropyl (meth)acrylate, ordimethylaminopropyl (meth)acrylamide.

Suitable cationic protonated amino and quaternary ammonium monomers, forinclusion in the cationic polymers of the composition herein, includevinyl compounds substituted with dialkylaminoalkyl acrylate,dialkylaminoalkyl methacrylate, monoalkylaminoalkyl acrylate,monoalkylaminoalkyl methacrylate, trialkyl methacryloxyalkyl ammoniumsalt, trialkyl acryloxyalkyl ammonium salt, diallyl quaternary ammoniumsalts, and vinyl quaternary ammonium monomers having cyclic cationicnitrogen-containing rings such as pyridinium, imidazolium, andquaternized pyrrolidone, e.g., alkyl vinyl imidazolium, alkyl vinylpyridinium, alkyl vinyl pyrrolidone salts.

Other suitable cationic polymers for use in the compositions includecopolymers of 1-vinyl-2-pyrrolidone and 1-vinyl-3-methylimidazolium salt(e.g., chloride salt) (referred to in the industry by the Cosmetic,Toiletry, and Fragrance Association, “CTFA”, as Polyquaternium-16);copolymers of 1-vinyl-2-pyrrolidone and dimethylaminoethyl methacrylate(referred to in the industry by CTFA as Polyquaternium-11); cationicdiallyl quaternary ammonium-containing polymers, including, for example,dimethyldiallylammonium chloride homopolymer, copolymers of acrylamideand dimethyldiallylammonium chloride (referred to in the industry byCTFA as Polyquaternium 6 and Polyquaternium 7, respectively); amphotericcopolymers of acrylic acid including copolymers of acrylic acid anddimethyldiallylammonium chloride (referred to in the industry by CTFA asPolyquaternium 22), terpolymers of acrylic acid withdimethyldiallylammonium chloride and acrylamide (referred to in theindustry by CTFA as Polyquaternium 39), and terpolymers of acrylic acidwith methacrylamidopropyl trimethylammonium chloride and methylacrylate(referred to in the industry by CTFA as Polyquaternium 47). Preferredcationic substituted monomers are the cationic substituteddialkylaminoalkyl acrylamides, dialkylaminoalkyl methacrylamides, andcombinations thereof. A non limiting example ispolymethyacrylamidopropyl trimonium chloride, available under thetradename Polycare 133, from Rhone-Poulenc.

Other suitable cationic polymers for use in the composition includepolysaccharide polymers, such as cationic cellulose derivatives andcationic starch derivatives.

Preferred cationic cellulose polymers are salts of hydroxyethylcellulose reacted with trimethyl ammonium substituted epoxide, referredto in the industry (CTFA) as Polyquaternium 10 and available fromAmerchol Corp. in their Polymer LR, JR, and KG series of polymers. Othersuitable types of cationic cellulose include the polymeric quaternaryammonium salts of hydroxyethyl cellulose reacted with lauryl dimethylammonium-substituted epoxide referred to in the industry (CTFA) asPolyquaternium 24. These materials are available from Amerchol Corp.under the tradename Polymer LM-200.

Other suitable cationic polymers include cationic guar gum derivatives,such as guar hydroxypropyltrimonium chloride, specific examples of whichinclude the Jaguar series commercially available from Rhone-PoulencIncorporated and the N-Hance series commercially available from AqualonDivision of Hercules, Inc. Other suitable cationic polymers includequaternary nitrogen-containing cellulose ethers, some examples of whichare described in U.S. Pat. No. 3,962,418. Other suitable cationicpolymers include copolymers of etherified cellulose, guar and starch,some examples of which are described in U.S. Pat. No. 3,958,581. Whenused, the cationic polymers herein are either soluble in the compositionor are soluble in a complex coacervate phase in the composition formedby the cationic polymer and the anionic, amphoteric and/or zwitterionicdetersive surfactant component described hereinbefore. Complexcoacervates of the cationic polymer can also be formed with othercharged materials in the composition.

b. Anionic Polymers

Examples of anionic polymers are copolymers of vinyl acetate andcrotonic acid, terpolymers of vinyl acetate, crotonic acid and a vinylester of an alpha-branched saturated aliphatic monocarboxylic acid suchas vinyl neodecanoate; and copolymers of methyl vinyl ether and maleicanhydride, acrylic copolymers and terpolymers containing acrylic acid ormethacrylic acid.

Examples of anionic monomers include unsaturated carboxylic acidmonomers such as acrylic acid, methacrylic acid, maleic acid, maleicacid half ester, itaconic acid, fumeric acid, and crotonic acid; halfesters of an unsaturated polybasic acid anhydride such as succinicanhydride, phthalic anhydride or the like with a hydroxylgroup-containing acrylate and/or methacrylate such as hydroxyethylacrylate and, hydroxyethyl methacrylate, hydroxypropyl acrylate and thelike; monomers having a sulfonic acid group such as styrenesulfonicacid, sulfoethyl acrylate and methacrylate, and the like; and monomershaving a phosphoric acid group such as acid phosphooxyethyl acrylate andmethacrylate, 3-chloro-2-acid phosphooxypropyl acrylate andmethacrylate, and the like.

c. Amphoteric Monomers

Examples of the amphoteric monomers include zwitterionized derivativesof the aforementioned amine derivatives of (meth)acrylic acids or theamine derivatives of (meth)acrylamide such as dimethylaminoethyl(meth)acrylate, dimethylaminopropyl(meth)acrylamide by a halogenatedfatty acid salt such as potassium monochloroacetate, sodiummonobromopropionate, aminomethylpropanol salt of monochloroacetic acid,triethanolamine salts of monochloroacetic acid and the like; and aminederivatives of (meth)acrylic acid or (meth)acrylamide, as discussedabove, modified with propanesultone.

34. Nonionic Polymers

The compositions herein can comprise nonionic polymers. For instance,polyalkylene glycols having a molecular weight of more than about 1000can be used. Preferred polyethylene glycol polymers can include PEG-2M(also known as Polyox WSR® N-10, which is available from Union Carbideand as PEG-2,000); PEG-5M (also known as Polyox WSR® N-35 and PolyoxWSR® N-80, available from Union Carbide and as PEG-5,000 andPolyethylene Glycol 300,000); PEG-7M (also known as Polyox WSR® N-750available from Union Carbide); PEG-9M (also known as Polyox WSR® N-3333available from Union Carbide); and PEG-14 M (also known as Polyox WSR®N-3000 available from Union Carbide).

Examples of nonionic monomers are acrylic or methacrylic acid esters ofC1-C24 alcohols, such as methanol, ethanol, 1-propanol, 2-propanol,1-butanol, 2-methyl-1-propanol, 1-pentanol, 2-pentanol, 3-pentanol,2-methyl-1-butanol, 1-methyl-1-butanol, 3-methyl-1-butanol,1-methyl-1-pentanol, 2-methyl-1-pentanol, 3-methyl-1-pentanol,t-butanol, cyclohexanol, 2-ethyl-1-butanol, 3-heptanol, benzyl alcohol,2-octanol, 6-methyl-1-heptanol, 2-ethyl-1-hexanol,3,5-dimethyl-1-hexanol, 3,5,5-trimethyl-1-hexanol, 1-decanol,1-dodecanol, 1-hexadecanol, 1-octadecanol, styrene, chlorostyrene, vinylesters such as vinyl acetate, vinyl chloride, vinylidene chloride,acrylonitrile, alpha-methylstyrene, t-butylstyrene, butadiene,cyclohexadiene, ethylene, propylene, vinyl toluene, alkoxyalkyl(meth)acrylate, methoxy ethyl (meth)acrylate, butoxyethyl(meth)acrylate, allyl acrylate, allyl methacrylate, cyclohexyl acrylateand methacrylate, oleyl acrylate and methacrylate, benzyl acrylate andmethacrylate, tetrahydrofurfuryl acrylate and methacrylate, ethyleneglycol di-acrylate and -methacrylate, 1,3-butyleneglycol di-acrylate and-methacrylate, diacetonacrylamide, isobornyl (meth)acrylate, n-butylmethacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, methylmethacrylate, t-butylacrylate, t-butylmethacrylate, and mixtures thereof

35. Hair Conditioning Agents

Conditioning agents include any material which is used to give aparticular conditioning benefit to keratinous tissue. For instance, inhair treatment compositions, suitable conditioning agents include thosewhich deliver one or more benefits relating to shine, softness,combability, antistatic properties, wet-handling, damage, manageability,body, and greasiness. Conditioning agents useful in the compositions ofthe present invention can comprise a water insoluble, water dispersible,non-volatile liquid that forms emulsified, liquid particles. Suitableconditioning agents for use in the composition include thoseconditioning agents characterized generally as silicones (e.g., siliconeoils, cationic silicones, silicone gums, high refractive silicones, andsilicone resins), organic conditioning oils (e.g., hydrocarbon oils,polyolefins, and fatty esters) or combinations thereof, or thoseconditioning agents which otherwise form liquid, dispersed particles inthe aqueous surfactant matrix herein.

When included, the concentration of the conditioning agent in thecomposition can be sufficient to provide the desired conditioningbenefits, and as will be apparent to one of ordinary skill in the art.Such concentration can vary with the conditioning agent, theconditioning performance desired, the average size of the conditioningagent particles, the type and concentration of other components, andother like factors.

a. Silicones

The conditioning agent of the compositions of the present invention ispreferably an insoluble silicone conditioning agent. The siliconeconditioning agent particles may comprise volatile silicone,non-volatile silicone, or combinations thereof. Preferred arenon-volatile silicone conditioning agents. If volatile silicones arepresent, it will typically be incidental to their use as a solvent orcarrier for commercially available forms of non-volatile siliconematerials ingredients, such as silicone gums and resins. The siliconeconditioning agent particles may comprise a silicone fluid conditioningagent and may also comprise other ingredients, such as a silicone resinto improve silicone fluid deposition efficiency or enhance glossiness ofthe hair.

The concentration of the silicone conditioning agent typically rangesfrom about 0.01% to about 10%, preferably from about 0.1% to about 8%,more preferably from about 0.1% to about 5%, more preferably from about0.2% to about 3%. Non-limiting examples of suitable siliconeconditioning agents, and optional suspending agents for the silicone,are described in U.S. Reissue Pat. No. 34,584, U.S. Pat. No. 5,104,646,and U.S. Pat. No. 5,106,609.

Background material on silicones including sections discussing siliconefluids, gums, and resins, as well as manufacture of silicones, are foundin Encyclopedia of Polymer Science and Engineering, vol. 15, 2d ed., pp204-308, John Wiley & Sons, Inc. (1989).

b. Silicone Oils

Silicone fluids include silicone oils, which are flowable siliconematerials having a viscosity, as measured at 25° C., less than 1,000,000csk, preferably from about 5 csk to about 1,000,000 csk, more preferablyfrom about 100 csk to about 600,000 csk. Suitable silicone oils for usein the compositions of the present invention include polyalkylsiloxanes, polyaryl siloxanes, polyalkylaryl siloxanes, polyethersiloxane copolymers, and mixtures thereof. Other insoluble, non-volatilesilicone fluids having hair conditioning properties may also be used.

c. Amino and Cationic Silicones

Cationic silicone fluids suitable for use in the compositions of thepresent invention include, but are not limited to, the polymer known as“trimethylsilylamodimethicone”. Other silicone cationic polymers whichmay be used in the compositions of the present invention may be UCARESILICONE ALE 56™, available from Union Carbide.

d. Silicone Gums

Other silicone fluids suitable for use in the compositions of thepresent invention are the insoluble silicone gums. These gums arepolyorganosiloxane materials having a viscosity, as measured at 25° C.,of greater than or equal to 1,000,000 csk. Silicone gums are describedin U.S. Pat. No. 4,152,416; Noll and Walter, Chemistry and Technology ofSilicones, New York: Academic Press (1968); and in General ElectricSilicone Rubber Product Data Sheets SE 30, SE 33, SE 54 and SE 76.Specific non-limiting examples of silicone gums for use in thecompositions of the present invention include polydimethylsiloxane,(polydimethylsiloxane) (methylvinylsiloxane) copolymer,poly(dimethylsiloxane) (diphenyl siloxane) (methylvinylsiloxane)copolymer and mixtures thereof.

e. High Refractive Index Silicones

Other non-volatile, insoluble silicone fluid conditioning agents thatare suitable for use in the compositions of the present invention arethose known as “high refractive index silicones,” having a refractiveindex of at least about 1.46, preferably at least about 1.48, morepreferably at least about 1.52, more preferably at least about 1.55. Therefractive index of the polysiloxane fluid will generally be less thanabout 1.70, typically less than about 1.60. In this context,polysiloxane “fluid” includes oils as well as gums.

When high refractive index silicones are used in the compositions of thepresent invention, they are preferably used in solution with a spreadingagent, such as a silicone resin or a surfactant, to reduce the surfacetension by a sufficient amount to enhance spreading and thereby enhancethe glossiness (subsequent to drying) of hair treated with thecompositions.

Silicone fluids suitable for use in the compositions of the presentinvention are disclosed in U.S. Pat. No. 2,826,551, U.S. Pat. No.3,964,500, U.S. Pat. No. 4,364,837, British Pat. No. 849,433, andSilicon Compounds, Petrarch Systems, Inc. (1984).

f. Silicone Resins

Silicone resins may be included in the silicone conditioning agent ofthe compositions of the present invention. These resins are highlycross-linked polymeric siloxane systems. The cross-linking is introducedthrough the incorporation of trifunctional and tetrafunctional silaneswith monofunctional or difunctional, or both, silanes during manufactureof the silicone resin.

36. Organic Conditioning Oils

Compositions of the present invention may also comprise organicconditioning oil. In one embodiment, from about 0.05% to about 20%,preferably from about 0.08% to about 1.5%, more preferably from about0.1% to about 1%, of at least one organic conditioning oil is includedas a conditioning agent, either alone or in combination with otherconditioning agents, such as the silicones (described herein).

a. Hydrocarbon Oils

Suitable organic conditioning oils for use as conditioning agents in thecompositions of the present invention include, but are not limited to,hydrocarbon oils having at least about 10 carbon atoms, such as cyclichydrocarbons, straight chain aliphatic hydrocarbons (saturated orunsaturated), and branched chain aliphatic hydrocarbons (saturated orunsaturated), including polymers and mixtures thereof. Straight chainhydrocarbon oils preferably are from about C12 to about C19. Branchedchain hydrocarbon oils, including hydrocarbon polymers, typically willcontain more than 19 carbon atoms.

Specific non-limiting examples of these hydrocarbon oils includeparaffin oil, mineral oil, saturated and unsaturated dodecane, saturatedand unsaturated tridecane, saturated and unsaturated tetradecane,saturated and unsaturated pentadecane, saturated and unsaturatedhexadecane, polybutene, polydecene, and mixtures thereof. Branched-chainisomers of these compounds, as well as of higher chain lengthhydrocarbons, can also be used, examples of which include highlybranched, saturated or unsaturated, alkanes such as thepermethyl-substituted isomers, e.g., the permethyl-substituted isomersof hexadecane and eicosane, such as2,2,4,4,6,6,8,8-dimethyl-10-methylundecane and2,2,4,4,6,6-dimethyl-8-methylnonane, available from PermethylCorporation, hydrocarbon polymers such as polybutene and polydecene. Apreferred hydrocarbon polymer is polybutene, such as the copolymer ofisobutylene and butene. A commercially available material of this typeis L-14 polybutene from Amoco Chemical Corporation. Another example ishydrogenated polyisobute or liquid isoparaffine.

b. Polyolefins

Organic conditioning oils for use in the compositions of the presentinvention can also include liquid polyolefins, more preferably liquidpoly-α-olefins, more preferably hydrogenated liquid poly-α-olefins.Polyolefins for use herein are prepared by polymerization of C4 to aboutC14 olefenic monomers, preferably from about C6 to about C12.

Preferred non-limiting examples of olefenic monomers for use inpreparing the polyolefin liquids herein include ethylene, propylene,1-butene, 1-pentene, 1-hexene to 1-hexadecenes, 1-octene, 1-decene,1-dodecene, 1-tetradecene, branched chain isomers such as4-methyl-1-pentene, and mixtures thereof. Also suitable for preparingthe polyolefin liquids are olefin-containing refinery feedstocks oreffluents.

c. Fatty Esters

Other suitable organic conditioning oils for use as the conditioningagent in the compositions of the present invention include, but are notlimited to, fatty esters having at least 10 carbon atoms. These fattyesters include esters with hydrocarbyl chains derived from fatty acidsor alcohols (e.g. mono-esters, polyhydric alcohol esters, and di- andtri-carboxylic acid esters). The hydrocarbyl radicals of the fattyesters hereof may include or have covalently bonded thereto othercompatible functionalities, such as amides and alkoxy moieties (e.g.,ethoxy or ether linkages, etc.).

Specific examples of preferred fatty esters include, but are not limitedto: isopropyl isostearate, hexyl laurate, isohexyl laurate, isohexylpalmitate, isopropyl palmitate, decyl oleate, isodecyl oleate, hexadecylstearate, decyl stearate, isopropyl isostearate, dihexyldecyl adipate,lauryl lactate, myristyl lactate, cetyl lactate, oleyl stearate, oleyloleate, oleyl myristate, lauryl acetate, cetyl propionate, and oleyladipate.

Other fatty esters suitable for use in the compositions of the presentinvention are mono-carboxylic acid esters of the general formula R′COOR,wherein R′ and R are alkyl or alkenyl radicals, and the sum of carbonatoms in R′ and R is at least 10, preferably at least 22.

Still other fatty esters suitable for use in the compositions of thepresent invention are di- and tri-alkyl and alkenyl esters of carboxylicacids, such as esters of C₄ to C₈ dicarboxylic acids (e.g. C₁ to C₂₂esters, preferably C₁ to C₆, of succinic acid, glutaric acid, and adipicacid). Specific non-limiting examples of di- and tri-alkyl and alkenylesters of carboxylic acids include isocetyl stearyol stearate,diisopropyl adipate, and tristearyl citrate.

Other fatty esters suitable for use in the compositions of the presentinvention are those known as polyhydric alcohol esters. Such polyhydricalcohol esters include alkylene glycol esters, such as ethylene glycolmono and di-fatty acid esters, diethylene glycol mono- and di-fatty acidesters, polyethylene glycol mono- and di-fatty acid esters, propyleneglycol mono- and di-fatty acid esters, polypropylene glycol monooleate,polypropylene glycol 2000 monostearate, ethoxylated propylene glycolmonostearate, glyceryl mono- and di-fatty acid esters, polyglycerolpoly-fatty acid esters, ethoxylated glyceryl monostearate, 1,3-butyleneglycol monostearate, 1,3-butylene glycol distearate, polyoxyethylenepolyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylenesorbitan fatty acid esters.

Still other fatty esters suitable for use in the compositions of thepresent invention are glycerides, including, but not limited to, mono-,di-, and tri-glycerides, preferably di- and tri-glycerides, morepreferably triglycerides. For use in the compositions described herein,the glycerides are preferably the mono-, di-, and tri-esters of glyceroland long chain carboxylic acids, such as C₁₀ to C₂₂ carboxylic acids. Avariety of these types of materials can be obtained from vegetable andanimal fats and oils, such as castor oil, safflower oil, cottonseed oil,corn oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil,sesame oil, lanolin and soybean oil. Synthetic oils include, but are notlimited to, triolein and tristearin glyceryl dilaurate.

Other fatty esters suitable for use in the compositions of the presentinvention are water insoluble synthetic fatty esters.

Specific non-limiting examples of suitable synthetic fatty esters foruse in the compositions of the present invention include: P-43 (C₈-C₁₀triester of trimethylolpropane), MCP-684 (tetraester of 3,3diethanol-1,5 pentadiol), MCP 121 (C₈-C₁₀ diester of adipic acid), allof which are available from Mobil Chemical Company.

37. Anti-Dandruff Actives

The compositions of the present invention may also contain ananti-dandruff agent. Suitable, non-limiting examples of anti-dandruffparticulates include: pyridinethione salts, azoles, selenium sulfide,particulate sulfur, and mixtures thereof. Preferred are pyridinethionesalts, especially 1-hydroxy-2-pyridinethione salts. The concentration ofpyridinethione anti-dandruff particulate typically ranges from about0.1% to about 4%, by weight of the composition, preferably from about0.1% to about 3%, more preferably from about 0.3% to about 2%. Preferredpyridinethione salts include those formed from heavy metals such aszinc, tin, cadmium, magnesium, aluminum and zirconium, preferably zinc,more preferably the zinc salt of 1-hydroxy-2-pyridinethione (known as“zinc pyridinethione” or “ZPT”). Pyridinethione anti-dandruff agents aredescribed, for example, in U.S. Pat. No. 2,809,971; U.S. Pat. No.3,236,733; U.S. Pat. No. 3,753,196; U.S. Pat. No. 3,761,418; U.S. Pat.No. 4,345,080; U.S. Pat. No. 4,323,683; U.S. Pat. No. 4,379,753; andU.S. Pat. No. 4,470,982.

38. Humectant

The compositions of the present invention may contain a humectant.Humectants can be selected from the group consisting of polyhydricalcohols, water soluble alkoxylated nonionic polymers, and mixturesthereof. Humectants, when used herein, are preferably used at levels offrom about 0.1% to about 20%, more preferably from about 0.5% to about5%.

Polyhydric alcohols useful herein include glycerin, sorbitol, propyleneglycol, butylene glycol, hexylene glycol, ethoxylated glucose,1,2-hexane diol, hexanetriol, dipropylene glycol, erythritol, trehalose,diglycerin, xylitol, maltitol, maltose, glucose, fructose, sodiumchondroitin sulfate, sodium hyaluronate, sodium adenosine phosphate,sodium lactate, pyrrolidone carbonate, glucosamine, cyclodextrin, andmixtures thereof.

Water soluble alkoxylated nonionic polymers useful herein includepolyethylene glycols and polypropylene glycols having a molecular weightof up to about 1000 such as PEG-200, PEG-400, PEG-600, PEG-1000 (CTFAnames), and mixtures thereof.

39. Suspending Agent

The compositions of the present invention may further comprise asuspending agent, preferably at concentrations effective for suspendingwater-insoluble material in dispersed form in the compositions or formodifying the viscosity of the composition. Such concentrations canpreferably range from about 0.1% to about 10%, more preferably fromabout 0.3% to about 5.0%.

Suspending agents useful herein include anionic polymers and nonionicpolymers. Useful herein are vinyl polymers such as cross linked acrylicacid polymers with the CTFA name Carbomer, cellulose derivatives andmodified cellulose polymers such as methyl cellulose, ethyl cellulose,nitro cellulose, sodium carboxymethyl cellulose, crystalline cellulose,cellulose powder, polyvinylpyrrolidone, polyvinyl alcohol, guar gum,hydroxypropyl guar gum, arabia gum, galactan, carob gum, pectin, agar,quince seed (Cydonia oblonga Mill), starch (rice, corn, potato, wheat),algae colloids (algae extract), microbiological polymers such asdextran, succinoglucan, pulleran, starch-based polymers such ascarboxymethyl starch, methylhydroxypropyl starch, alginic acid-basedpolymers such as sodium alginate, alginic acid propylene glycol esters,acrylate polymers such as sodium polyacrylate, polyethylacrylate,polyacrylamide, polyethyleneimine, and inorganic water soluble materialsuch as bentonite, aluminum magnesium silicate, laponite, hectonite, andanhydrous silicic acid. Actives aforementioned as thickening agents canalso be used herein as suspending agents.

Commercially available viscosity modifiers highly useful herein includeCarbomers with tradenames Carbopol 934, Carbopol 940, Carbopol 950,Carbopol 980, and Carbopol 981, all available from B.F. GoodrichCompany, acrylates/steareth-20 methacrylate copolymer with tradenameACRYSOL 22 available from Rohm and Hass, nonoxynyl hydroxyethylcellulosewith tradename AMERCELL POLYMER HM-1500 available from Amerchol,methylcellulose with tradename BENECEL, hydroxyethyl cellulose withtradename NATROSOL, hydroxypropyl cellulose with tradename KLUCEL, cetylhydroxyethyl cellulose with tradename POLYSURF 67, all supplied byHercules, ethylene oxide and/or propylene oxide based polymers withtradenames CARBOWAX PEGs, POLYOX WASRs, and UCON FLUIDS, all supplied byAmerchol.

Other optional suspending agents include crystalline suspending agentswhich can be categorized as acyl derivatives, long chain amine oxides,long chain acyl derivatives and mixtures thereof. These suspendingagents are described in U.S. Pat. No. 4,741,855. These preferredsuspending agents include ethylene glycol esters of fatty acids, alkanolamides of fatty acids, long chain esters of long chain fatty acids(e.g., stearyl stearate, cetyl palmitate, etc.); long chain esters oflong chain alkanol amides (e.g., stearamide diethanolamide distearate,stearamide monoethanolamide stearate); and glyceryl esters (e.g.,glyceryl distearate, trihydroxystearin, tribehenin) a commercial exampleof which is Thixin® available from Rheox, Inc.

Other suitable suspending agents include primary amines having a fattyalkyl moiety having at least about 16 carbon atoms, examples of whichinclude palmitamine or stearamine, and secondary amines having two fattyalkyl moieties each having at least about 12 carbon atoms, examples ofwhich include dipalmitoylamine or di(hydrogenated tallow)amine. Stillother suitable suspending agents include di(hydrogenated tallow)phthalicacid amide, and crosslinked maleic anhydride-methyl vinyl ethercopolymer.

40. Terpene Alcohol

The compositions of the present invention may comprise a terpene alcoholor combinations of terpene alcohols. As used herein, “terpene alcohol”refers to organic compounds composed of two or more 5-carbon isopreneunits [CH2=C(CH3)-CH═CH2] with a terminal hydroxyl group. Preferably,the composition can comprise from about 0.001% to about 50%, preferablyfrom about 0.01% to about 20%, more preferably from about 0.1% to about15%, even more preferably from about 0.1% to about 10%, still morepreferably from about 0.5% to about 5%, and still more preferably fromabout 1% to about 5%, by weight of the composition, of the terpenealcohol.

Examples of terpene alcohols that can be useful herein include farnesol,derivatives of farnesol, isomers of farnesol, geraniol, derivatives ofgeraniol, isomers of geraniol, phytantriol, derivatives of phytantriol,isomers of phytantriol, and mixtures thereof. A preferred terpenealcohol for use herein is farnesol.

a. Farnesol and Derivatives Thereof.

Farnesol is a naturally occurring substance which is believed to act asa precursor and/or intermediate in the biosynthesis of squalene andsterols, especially cholesterol. Farnesol is also involved in proteinmodification and regulation (e.g., farnesylation of proteins), and thereis a cell nuclear receptor which is responsive to farnesol.

Chemically, farnesol is [2E,6E]-3,7,11-trimethyl-2,6,10-dodecatrien-1-oland as used herein “farnesol” includes isomers and tautomers of such.Farnesol is commercially available, e.g., under the names farnesol (amixture of isomers from Dragoco) and trans-trans-farnesol (SigmaChemical Company). A suitable derivative of farnesol is farnesyl acetatewhich is commercially available from Aldrich Chemical Company.

b. Geraniol and Derivatives Thereof.

Geraniol is the common name for the chemical known as3,7-dimethyl-2,6-octadien-1-ol. As used herein, “geraniol” includesisomers and tautomers of such. Geraniol is commercially available fromAldrich Chemical Company. Suitable derivatives of geraniol includegeranyl acetate, geranylgeraniol, geranyl pyrophosphate, andgeranylgeranyl pyrophosphate, all of which are commercially availablefrom Sigma Chemical Company. For example, geraniol is useful as a spidervessel/red blotchiness repair agent, a dark circle/puffy eye repairagent, sallowness repair agent, a sagging repair agent, an anti-itchagent, a skin thickening agent, a pore reduction agent, oil/shinereduction agent, a post-inflammatory hyperpigmentation repair agent,wound treating agent, an anti-cellulite agent, and regulating skintexture, including wrinkles and fine lines.

c. Phytantriol and Derivatives Thereof.

Phytantriol is the common name for the chemical known as 3,7,11,15tetramethylhexadecane-1,2,3,-triol. Phytantriol is commerciallyavailable from BASF. For example, phytantriol is useful as a spidervessel/red blotchiness repair agent, a dark circle/puffy eye repairagent, sallowness repair agent, a sagging repair agent, an anti-itchagent, a skin thickening agent, a pore reduction agent, oil/shinereduction agent, a post-inflammatory hyperpigmentation repair agent,wound treating agent, an anti-cellulite agent, and regulating skintexture, including wrinkles and fine lines.

41. Enzymes, Enzyme Inhibitors and Enzyme Activators (Coenzymes)

The compositions of the present invention may contain a safe andeffective amount of one or more enzymes, enzyme inhibitors or enzymeactivators (coenzymes). Examples of enzymes are lipases, proteases,catalase, superoxide-dismutase, amylases, glucuronidases, peroxidases,in particular glutathione peroxidase or lactoperoxidase, ceramidases,hyaluronidases. All of these enzymes may be obtained by extraction or byfermentation biotechnology processes. Examples of enzyme inhibitorsinclude trypsine inhibitors, Bowmann Birk inhibitor, chymotrypsininhibitors, botanical extracts with or without tannins, flavonoids,quercetin which inhibit enzymatic activity. Enzyme preparations can befound, for instance, in the product named VENUCEANE proposed by SEDERMA,France (WO 02/066668). Enzyme activators and coenzymes include CoenzymeA, coenzyme Q10 (ubiquinone), glycyrrhizidine, berberine, chrysine.

II CARRIER

The compositions of the present invention can comprise an orally or adermatologically acceptable carrier, or injectible liquid, dependingupon the desired product form.

A. Dermatologically Acceptable Carrier

The topical compositions of the present invention can also comprise adermatologically acceptable carrier for the composition. In oneembodiment, the carrier is present at a level of from about 50% to about99.99%, preferably from about 60% to about 99.9%, more preferably fromabout 70% to about 98%, and even more preferably from about 80% to about95%, by weight of the composition.

The carrier can be in a wide variety of forms. Non-limiting examplesinclude simple solutions (water or oil based), emulsions, and solidforms (gels, sticks). For example, emulsion carriers can include, butare not limited to, oil-in-water, water-in-oil, water-in-silicone,water-in-oil-in-water, and oil-in-water-in-silicone emulsions.

Depending upon the desired product form, preferred carriers can comprisean emulsion such as oil-in-water emulsions (e.g., silicone in water) andwater-in-oil emulsions, (e.g., water-in-silicone emulsions). As will beunderstood by the skilled artisan, a given component will distributeprimarily into either the water or oil phase, depending on the watersolubility/dispensability of the component in the composition. In oneembodiment, oil-in-water emulsions are especially preferred.

Emulsions according to the present invention can contain an aqueousphase and a lipid or oil. Lipids and oils may be derived from animals,plants, or petroleum and may be natural or synthetic (i.e., man-made).Preferred emulsions can also contain a humectant, such as glycerin.Emulsions can further comprise from about 0.1% to about 10%, morepreferably from about 0.2% to about 5%, of an emulsifier, based on theweight of the composition. Emulsifiers may be nonionic, anionic orcationic. Suitable emulsifiers are disclosed in, for example, U.S. Pat.No. 3,755,560, U.S. Pat. No. 4,421,769, and McCutcheon's Detergents andEmulsifiers, North American Edition, pages 317-324 (1986). Suitableemulsions may have a wide range of viscosities, depending on the desiredproduct form.

The compositions of the present invention can be in the form of pourableliquids (under ambient conditions). The compositions can thereforecomprise an aqueous carrier, which is typically present at a level offrom about 20% to about 95%, preferably from about 60% to about 85%. Theaqueous carrier may comprise water, or a miscible mixture of water andorganic solvent, but preferably comprises water with minimal or nosignificant concentrations of organic solvent, except as otherwiseincidentally incorporated into the composition as minor ingredients ofother essential or optional components.

The emulsion may also contain an anti-foaming agent to minimize foamingupon application to the keratinous tissue. Anti-foaming agents includehigh molecular weight silicones and other materials well known in theart for such use.

Preferred water-in-silicone and oil-in-water emulsions are described ingreater detail below.

1. Water-in-Silicone Emulsion

Water-in-silicone emulsions can contain a continuous silicone phase anda dispersed aqueous phase.

a. Continuous Silicone Phase

Preferred water-in-silicone emulsions of the present invention cancontain from about 1% to about 60%, preferably from about 5% to about40%, more preferably from about 10% to about 20%, by weight of acontinuous silicone phase. The continuous silicone phase exists as anexternal phase that contains or surrounds the discontinuous aqueousphase described hereinafter.

The continuous silicone phase contains a polyorganosiloxane oil. Apreferred water-in-silicone emulsion system is formulated to provide anoxidatively stable vehicle for the active ingredients of the presentinvention. The continuous silicone phase of these preferred emulsionscontain between about 50% and about 99.9% by weight oforganopolysiloxane oil and less than about 50% by weight of anon-silicone oil. In an especially preferred embodiment, the continuoussilicone phase contains at least about 50%, preferably from about 60% toabout 99.9%, more preferably from about 70% to about 99.9%, and evenmore preferably from about 80% to about 99.9%, polyorganosiloxane oil byweight of the continuous silicone phase, and up to about 50%non-silicone oils, preferably less about 40%, more preferably less thanabout 30%, even more preferably less than about 10%, and even morepreferably less than about 2%, by weight of the continuous siliconephase.

The organopolysiloxane oil for use in the composition may be volatile,non-volatile, or a mixture of volatile and non-volatile silicones. Theterm “nonvolatile” as used in this context refers to those siliconesthat are liquid under ambient conditions and have a flash point (underone atmospheric of pressure) of or greater than about 100° C. The term“volatile” as used in this context refers to all other silicone oils.Suitable organopolysiloxanes can be selected from a wide variety ofsilicones spanning a broad range of volatilities and viscosities.Examples of suitable organopolysiloxane oils include polyalkylsiloxanes,cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes.

Polyalkylsiloxanes useful in the composition herein includepolyalkylsiloxanes with viscosities of from about 0.5 to about 1,000,000centistokes at 25° C. Commercially available polyalkylsiloxanes includethe polydimethylsiloxanes, which are also known as dimethicones,examples of which include the Vicasil® series sold by General ElectricCompany and the Dow Corning® 200 series sold by Dow Corning Corporation.Specific examples of suitable polydimethylsiloxanes include Dow Corning®200 fluid, Dow Corning® 225 fluid, and Dow Corning® 200 fluids Examplesof suitable alkyl-substituted dimethicones include cetyl dimethicone andlauryl dimethicone.

Cyclic polyalkylsiloxanes suitable for use in the composition includecommercially available cyclomethicones such as Dow Corning® 244 fluid,Dow Corning® 344 fluid, Dow Corning® 245 fluid and Dow Corning® 345fluid.

Also useful are materials such as trimethylsiloxysilicate. Acommercially available trimethylsiloxysilicate is sold as a mixture withdimethicone as Dow Corning® 593 fluid. Dimethiconols are also suitablefor use in the composition. Commercially available dimethiconols aretypically sold as mixtures with dimethicone or cyclomethicone (e.g. DowCorning® 1401, 1402, and 1403 fluids).

Polyalkylaryl siloxanes are also suitable for use in the composition.Polymethylphenyl siloxanes having viscosities from about 15 to about 65centistokes at 25° C. are especially useful.

Preferred for use herein are organopolysiloxanes selected frompolyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones,trimethylsiloxysilicates, dimethiconols, polyalkylaryl siloxanes, andmixtures thereof. More preferred for use herein are polyalkylsiloxanesand cyclomethicones. Preferred among the polyalkylsiloxanes aredimethicones.

As stated above, the continuous silicone phase may contain one or morenon-silicone oils. Suitable non-silicone oils have a melting point ofabout 25° C. or less under about one atmosphere of pressure. Examples ofnon-silicone oils suitable for use in the continuous silicone phase arethose well known in the chemical arts in topical personal care productsin the form of water-in-oil emulsions, e.g., mineral oil, vegetableoils, synthetic oils, semisynthetic oils, etc.

b. Dispersed Aqueous Phase

The topical compositions of the present invention can contain from about30% to about 90%, more preferably from about 50% to about 85%, and stillmore preferably from about 70% to about 80% of a dispersed aqueousphase. In emulsion technology, the term “dispersed phase” is a termwell-known to one skilled in the art which means that the phase existsas small particles or droplets that are suspended in and surrounded by acontinuous phase. The dispersed phase is also known as the internal ordiscontinuous phase. The dispersed aqueous phase is a dispersion ofsmall aqueous particles or droplets suspended in and surrounded by thecontinuous silicone phase described hereinbefore.

The aqueous phase can be water, or a combination of water and one ormore water soluble or dispersible ingredients. Nonlimiting examples ofsuch ingredients include thickeners, acids, bases, salts, chelatingingredients, gums, water-soluble or dispersible alcohols and polyols,buffers, preservatives, sunscreening agents, colorings, and the like.

The topical compositions of the present invention will typically containfrom about 25% to about 90%, preferably from about 40% to about 80%,more preferably from about 60% to about 80%, water in the dispersedaqueous phase by weight of the composition.

c. Emulsifier for Dispersing the Aqueous Phase

The water-in-silicone emulsions of the present invention may preferablycontain an emulsifier. In a preferred embodiment, the compositioncontains from about 0.1% to about 10% emulsifier, more preferably fromabout 0.5% to about 7.5%, still more preferably from about 1% to about5%, emulsifier by weight of the composition. The emulsifier helpsdisperse and suspend the aqueous phase within the continuous siliconephase.

A wide variety of emulsifying agents can be employed herein to form thepreferred water-in-silicone emulsion. Known or conventional emulsifyingagents can be used in the composition, provided that the selectedemulsifying agent is chemically and physically compatible withcomponents of the composition of the present invention, and provides thedesired dispersion characteristics. Suitable emulsifiers includesilicone emulsifiers, non-silicon-containing emulsifiers, and mixturesthereof, known by those skilled in the art for use in topical personalcare products. Preferably these emulsifiers have an HLB value of or lessthan about 14, more preferably from about 2 to about 14, and still morepreferably from about 4 to about 14. Emulsifiers having an HLB valueoutside of these ranges can be used in combination with otheremulsifiers to achieve an effective weighted average HLB for thecombination that falls within these ranges.

Silicone emulsifiers are preferred. A wide variety of siliconeemulsifiers are useful herein. These silicone emulsifiers are typicallyorganically modified organopolysiloxanes, also known to those skilled inthe art as silicone surfactants. Useful silicone emulsifiers includedimethicone copolyols. These materials are polydimethyl siloxanes whichhave been modified to include polyether side chains such as polyethyleneoxide chains, polypropylene oxide chains, mixtures of these chains, andpolyether chains containing moieties derived from both ethylene oxideand propylene oxide. Other examples include alkyl-modified dimethiconecopolyols, i.e., compounds which contain C2-C30 pendant side chains.Still other useful dimethicone copolyols include materials havingvarious cationic, anionic, amphoteric, and zwitterionic pendantmoieties.

Nonlimiting examples of dimethicone copolyols and other siliconesurfactants useful as emulsifiers herein include polydimethylsiloxanepolyether copolymers with pendant polyethylene oxide side chains,polydimethylsiloxane polyether copolymers with pendant polypropyleneoxide side chains, polydimethylsiloxane polyether copolymers withpendant mixed polyethylene oxide and polypropylene oxide side chains,polydimethylsiloxane polyether copolymers with pendant mixedpoly(ethylene)(propylene)oxide side chains, polydimethylsiloxanepolyether copolymers with pendant organobetaine sidechains,polydimethylsiloxane polyether copolymers with pendant carboxylatesidechains, polydimethylsiloxane polyether copolymers with pendantquaternary ammonium sidechains; and also further modifications of thepreceding copolymers containing pendant C2-C30 straight, branched, orcyclic alkyl moieties. Examples of commercially available dimethiconecopolyols useful herein sold by Dow Corning Corporation are Dow Corning®190, 193, Q2-5220, 2501 Wax, 2-5324 fluid, and 3225C (this latermaterial being sold as a mixture with cyclomethicone). Cetyl dimethiconecopolyol is commercially available as a mixture with polyglyceryl-4isostearate (and) hexyl laurate and is sold under the tradename ABIL®WE-09 (available from Goldschmidt). Cetyl dimethicone copolyol is alsocommercially available as a mixture with hexyl laurate (and)polyglyceryl-3 oleate (and) cetyl dimethicone and is sold under thetradename ABIL® WS-08 (also available from Goldschmidt). Othernonlimiting examples of dimethicone copolyols also include lauryldimethicone copolyol, dimethicone copolyol acetate, dimethicone copolyoladipate, dimethicone copolyolamine, dimethicone copolyol behenate,dimethicone copolyol butyl ether, dimethicone copolyol hydroxy stearate,dimethicone copolyol isostearate, dimethicone copolyol laurate,dimethicone copolyol methyl ether, dimethicone copolyol phosphate, anddimethicone copolyol stearate.

Dimethicone copolyol emulsifiers useful herein are described, forexample, in U.S. Pat. No. 4,960,764, EP 330,369. Among thenon-silicone-containing emulsifiers useful herein are various non-ionicand anionic emulsifying agents such as sugar esters and polyesters,alkoxylated sugar esters and polyesters, C1-C30 fatty acid esters ofC1-C30 fatty alcohols, alkoxylated derivatives of C1-C30 fatty acidesters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fattyalcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters ofpolyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylenefatty ether phosphates, fatty acid amides, acyl lactylates, soaps, andmixtures thereof. Other suitable emulsifiers are described, for example,in McCutcheon's, Detergents and Emulsifiers, North American Edition(1986), published by Allured Publishing Corporation; U.S. Pat. No.5,011,681; U.S. Pat. No. 4,421,769; and U.S. Pat. No. 3,755,560.

Nonlimiting examples of these non-silicon-containing emulsifiersinclude: polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20),polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetylphosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate,Polysorbate 60, glyceryl stearate, PEG-100 stearate, polyoxyethylene 20sorbitan trioleate (Polysorbate 85), sorbitan monolaurate,polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methylglucose ether distearate, ceteth-10, diethanolamine cetyl phosphate,glyceryl stearate, PEG-100 stearate, and mixtures thereof.

d. Silicone Elastomer

The compositions of the present invention may also include from about0.1% to about 30%, by weight of the composition, of a silicone elastomercomponent. Preferably, the composition includes from about 1% to about30%, more preferably from about 2% to about 20%, by weight of thecomposition, of the silicone elastomer component.

Suitable for use herein are silicone elastomers, which can beemulsifying or non-emulsifying crosslinked siloxane elastomers ormixtures thereof. No specific restriction exists as to the type ofcurable organopolysiloxane composition that can serve as startingmaterial for the crosslinked organopolysiloxane elastomer. Examples inthis respect are addition reaction-curing organopolysiloxanecompositions which cure under platinum metal catalysis by the additionreaction between SiH-containing diorganopolysiloxane andorganopolysiloxane having silicon-bonded vinyl groups;condensation-curing organopolysiloxane compositions which cure in thepresence of an organotin compound by a dehydrogenation reaction betweenhydroxyl-terminated diorganopolysiloxane and SiH-containingdiorganopolysiloxane and condensation-curing organopolysiloxanecompositions which cure in the presence of an organotin compound or atitanate ester.

Addition reaction-curing organopolysiloxane compositions are preferredfor their rapid curing rates and excellent uniformity of curing. Aparticularly preferred addition reaction-curing organopolysiloxanecomposition is prepared from: a) an organopolysiloxane having at least 2lower alkenyl groups in each molecule; b) an organopolysiloxane havingat least 2 silicon-bonded hydrogen atoms in each molecule; and c) aplatinum-type catalyst.

The compositions of the present invention may include an emulsifyingcrosslinked organopolysiloxane elastomer, a non-emulsifying crosslinkedorganopolysiloxane elastomer, or a mixture thereof. The term“non-emulsifying,” as used herein, defines crosslinkedorganopolysiloxane elastomers from which polyoxyalkylene units areabsent. The term “emulsifying,” as used herein, means crosslinkedorganopolysiloxane elastomers having at least one polyoxyalkylene (e.g.,polyoxyethylene or polyoxypropylene) unit. Preferred emulsifyingelastomers herein include polyoxyalkylene modified elastomers formedfrom divinyl compounds, particularly siloxane polymers with at least twofree vinyl groups, reacting with Si—H linkages on a polysiloxanebackbone. Preferably, the elastomers are dimethyl polysiloxanescrosslinked by Si—H sites on a molecularly spherical MQ resin.Emulsifying crosslinked organopolysiloxane elastomers can notably bechosen from the crosslinked polymers described in U.S. Pat. Nos.5,412,004, 5,837,793, and 5,811,487. In addition, an emulsifyingelastomer comprised of dimethicone copolyol crosspolymer (and)dimethicone is available from Shin Etsu under the tradename KSG-21.

Advantageously, the non-emulsifying elastomers are dimethicone/vinyldimethicone crosspolymers. Such dimethicone/vinyl dimethiconecrosspolymers are supplied by a variety of suppliers including DowCorning (DC 9040 and DC 9041), General Electric (SFE 839), Shin Etsu(KSG-15, 16, 18 [dimethicone/phenyl vinyl dimethicone crosspolymer]),and Grant Industries (GRANSIL™ line of elastomers). Cross-linkedorganopolysiloxane elastomers useful in the present invention andprocesses for making them are further described in U.S. Pat. No.4,970,252, U.S. Pat. No. 5,760,116, and U.S. Pat. No. 5,654,362.

Commercially available elastomers preferred for use herein are DowCorning's 9040 silicone elastomer blend, Shin Etsu's KSG-21, andmixtures thereof.

e. Carrier for Silicone Elastomer

The topical compositions of the present invention may include from about1% to about 80%, by weight of the composition, of a suitable carrier forthe for the crosslinked organopolysiloxane elastomer component describedabove. The carrier, when combined with the cross-linkedorganopolysiloxane elastomer particles of the present invention, servesto suspend and swell the elastomer particles to provide an elastic,gel-like network or matrix. The carrier for the cross-linked siloxaneelastomer is liquid under ambient conditions, and preferably has a lowviscosity to provide for improved spreading on the skin.

Concentrations of the carrier in the cosmetic compositions of thepresent invention will vary primarily with the type and amount ofcarrier and the cross-linked siloxane elastomer employed. Preferredconcentrations of the carrier are from about 5% to about 50%, morepreferably from about 5% to about 40%, by weight of the composition.

The carrier for the cross-linked siloxane elastomer includes one or moreliquid carriers suitable for topical application to human skin. Theseliquid carriers may be organic, silicone-containing orfluorine-containing, volatile or non-volatile, polar or non-polar,provided that the liquid carrier forms a solution or other homogenousliquid or liquid dispersion with the selected cross-linked siloxaneelastomer at the selected siloxane elastomer concentration at atemperature of from about 28° C. to about 250° C., preferably from about28° C. to about 100° C., preferably from about 28° C. to about 78° C.The term “volatile” as used herein refers to all materials that are not“non-volatile” as previously defined herein. The phrase “relativelypolar” as used herein means more polar than another material in terms ofsolubility parameter; i.e., the higher the solubility parameter the morepolar the liquid. The term “non-polar” typically means that the materialhas a solubility parameter below about 6.5 (cal/cm3>) 05.

f. Non-Polar, Volatile Oils

The composition of the present invention may include non-polar, volatileoils. The non-polar, volatile oil tends to impart highly desirableaesthetic properties to the compositions of the present invention.Consequently, the non-polar, volatile oils are preferably utilized at afairly high level. Non-polar, volatile oils particularly useful in thepresent invention are silicone oils; hydrocarbons; and mixtures thereof.Such non-polar, volatile oils are disclosed, for example, in Cosmetics,Science, and Technology, Vol. 1, 27-104 edited by Balsam and Sagarin,1972. Examples of preferred non-polar, volatile hydrocarbons includepolydecanes such as isododecane and isodecane (e.g., Permethyl-99A whichis available from Presperse Inc.) and the C7-C8 through C12-C15isoparaffins (such as the Isopar Series available from Exxon Chemicals).Linear volatile silicones generally have a viscosity of less than about5 centistokes at 25° C., whereas the cyclic silicones have viscositiesof less than about 10 centistokes at 25° C. Highly preferred examples ofvolatile silicone oils include cyclomethicones of varying viscosities,e.g., Dow Corning 200, Dow Corning 244, Dow Corning 245, Dow Corning344, and Dow Corning 345, (commercially available from Dow CorningCorp.); SF-1204 and SF-1202 Silicone Fluids (commercially available fromG.E. Silicones), GE 7207 and 7158 (commercially available from GeneralElectric Co.); and SWS-03314 (commercially available from SWS SiliconesCorp.).

g. Relatively Polar, Non-Volatile Oils

The composition of the present invention may include relatively polar,non-volatile oils. The non-volatile oil is “relatively polar” ascompared to the non-polar, volatile oil discussed above. Therefore, thenon-volatile co-carrier is more polar (i.e., has a higher solubilityparameter) than at least one of the non-polar, volatile oils. Relativelypolar, non-volatile oils potentially useful in the present invention aredisclosed, for example, in Cosmetics, Science, and Technology, Vol. 1,27-104 edited by Balsam and Sagarin, 1972; U.S. Pat. Nos. 4,202,879 and4,816,261. Relatively polar, non-volatile oils useful in the presentinvention are preferably selected from silicone oils; hydrocarbon oils;fatty alcohols; fatty acids; esters of mono and dibasic carboxylic acidswith mono and polyhydric alcohols; polyoxyethylenes; polyoxypropylenes;mixtures of polyoxyethylene and polyoxypropylene ethers of fattyalcohols; and mixtures thereof.

h. Non-Polar, Non-Volatile Oils

In addition to the liquids discussed above, the carrier for thecross-linked siloxane elastomer may optionally include non-volatile,non-polar oils. Typical non-volatile, non-polar emollients aredisclosed, for example, in Cosmetics, Science, and Technology, Vol. 1,27-104 edited by Balsam and Sagarin, 1972; U.S. Pat. Nos. 4,202,879 and4,816,261. The non-volatile oils useful in the present invention areessentially non-volatile polysiloxanes, paraffinic hydrocarbon oils, andmixtures thereof.

2. Oil-in-Water Emulsions

Other preferred topical carriers include oil-in-water emulsions, havinga continuous aqueous phase and a hydrophobic, water-insoluble phase(“oil phase”) dispersed therein. The “oil phase” can contain oil,silicone or mixtures thereof, and includes but is not limited to theoils and silicones described above in the section on water-in-oilemulsions. The distinction of whether the emulsion is characterized asan oil-in-water or silicone-in-water emulsions is a function of whetherthe oil phase is composed of primarily oil or silicone. The water phaseof these emulsions consists primarily of water, but can also containvarious other ingredients such as those water phase ingredients listedin the above section on water-in-oil emulsion. The preferredoil-in-water emulsions comprises from about 25% to about 98%, preferablyfrom about 65% to about 95%, more preferably from about 70% to about 90%water by weight of the total composition.

In addition to a continuous water phase and dispersed oil or siliconephase, these oil-in-water compositions also comprise an emulsifier tostabilize the emulsion. Emulsifiers useful herein are well known in theart, and include nonionic, anionic, cationic, and amphotericemulsifiers. Non-limiting examples of emulsifiers useful in theoil-in-water emulsions of this invention are given in McCutcheon's,Detergents and Emulsifiers, North American Edition (1986), U.S. Pat. No.5,011,681; U.S. Pat. No. 4,421,769; and U.S. Pat. No. 3,755,560.Examples of suitable oil-in-water emulsion carriers are described inU.S. Pat. No. 5,073,371, and U.S. Pat. No. 5,073,372. An especiallypreferred oil-in-water emulsion, containing a structuring agent,hydrophilic surfactant and water, is described in detail hereinafter.

a. Structuring Agent

A preferred oil-in-water emulsion contains a structuring agent to assistin the formation of a liquid crystalline gel network structure. Withoutbeing limited by theory, it is believed that the structuring agentassists in providing rheological characteristics to the compositionwhich contribute to the stability of the composition. The structuringagent may also function as an emulsifier or surfactant. Preferredcompositions of this invention contain from about 0.5% to about 20%,more preferably from about 1% to about 10%, even more preferably fromabout 1% to about 5%, by weight of the composition, of a structuringagent.

The preferred structuring agents of the present invention includestearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenylalcohol, the polyethylene glycol ether of stearyl alcohol having anaverage of about 1 to about 21 ethylene oxide units, the polyethyleneglycol ether of cetyl alcohol having an average of about 1 to about 5ethylene oxide units, and mixtures thereof. More preferred structuringagents of the present invention are selected from stearyl alcohol, cetylalcohol, behenyl alcohol, the polyethylene glycol ether of stearylalcohol having an average of about 2 ethylene oxide units (steareth-2),the polyethylene glycol ether of stearyl alcohol having an average ofabout 21 ethylene oxide units (steareth-21), the polyethylene glycolether of cetyl alcohol having an average of about 2 ethylene oxideunits, and mixtures thereof. Even more preferred structuring agents areselected from stearic acid, palmitic acid, stearyl alcohol, cetylalcohol, behenyl alcohol, steareth-2, steareth-21, and mixtures thereof.

b. Hydrophilic Surfactant

The preferred oil-in-water emulsions contain from about 0.05% to about10%, preferably from about 1% to about 6%, and more preferably fromabout 1% to about 3% of at least one hydrophilic surfactant which candisperse the hydrophobic materials in the water phase (percentages byweight of the topical carrier). The surfactant, at a minimum, must behydrophilic enough to disperse in water.

Preferred hydrophilic surfactants are selected from nonionicsurfactants. Among the nonionic surfactants that are useful herein arethose that can be broadly defined as condensation products of long chainalcohols, e.g. C8-30 alcohols, with sugar or starch polymers, i.e.,glycosides. These compounds can be represented by the formula (S)n-O—Rwherein S is a sugar moiety such as glucose, fructose, mannose, andgalactose; n is an integer of from about 1 to about 1000, and R is aC8-30 alkyl group. Examples of long chain alcohols from which the alkylgroup can be derived include decyl alcohol, cetyl alcohol, stearylalcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, and the like.Preferred examples of these surfactants include those wherein S is aglucose moiety, R is a C8-20 alkyl group, and n is an integer of fromabout 1 to about 9. Commercially available examples of these surfactantsinclude decyl polyglucoside (available as APG 325 CS from Henkel) andlauryl polyglucoside (available as APG 600 CS and 625 CS from Henkel).Other useful nonionic surfactants include the condensation products ofalkylene oxides with fatty acids (i.e. alkylene oxide esters of fattyacids), the condensation products of alkylene oxides with 2 moles offatty acids (i.e. alkylene oxide diesters of fatty acids), thecondensation products of alkylene oxides with fatty alcohols (i.e.alkylene oxide ethers of fatty alcohols), the condensation products ofalkylene oxides with both fatty acids and fatty alcohols [i.e. whereinthe polyalkylene oxide portion is esterified on one end with a fattyacid and etherified (i.e. connected via an ether linkage) on the otherend with a fatty alcohol]. Nonlimiting examples of these alkylene oxidederived nonionic surfactants include ceteth-6, ceteth-10, ceteth-12,ceteareth-6, ceteareth-10, ceteareth-12, steareth-6, steareth-10,steareth-12, steareth-21, PEG-6 stearate, PEG-10 stearate, PEG-100stearate, PEG-12 stearate, PEG-20 glyceryl stearate, PEG-80 glyceryltallowate, PEG-10 glyceryl stearate, PEG-30 glyceryl cocoate, PEG-80glyceryl cocoate, PEG-200 glyceryl tallowate, PEG-8 dilaurate, PEG-10distearate, and mixtures thereof.

Still other useful nonionic surfactants include polyhydroxy fatty acidamide surfactants. An especially preferred surfactant corresponding tothe above structure is coconut alkyl N-methyl glucoside amide. Processesfor making compositions containing polyhydroxy fatty acid amides aredisclosed, for example in U.S. Pat. No. 2,965,576; U.S. Pat. No.2,703,798, and U.S. Pat. No. 1,985,424.

Preferred among the nonionic surfactants are those selected from thegroup consisting of steareth-21, ceteareth-20, ceteareth-12, sucrosecocoate, steareth-100, PEG-100 stearate, and mixtures thereof.

Other nonionic surfactants suitable for use herein include sugar estersand polyesters, alkoxylated sugar esters and polyesters, C1-C30 fattyacid esters of C1-C30 fatty alcohols, alkoxylated derivatives of C1-C30fatty acid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30fatty alcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 estersof polyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylenefatty ether phosphates, fatty acid amides, acyl lactylates, and mixturesthereof. Nonlimiting examples of these emulsifiers include: polyethyleneglycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose etherdistearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetylphosphate, diethanolamine cetyl phosphate, Polysorbate 60, glycerylstearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85),sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate,polyglyceryl-4 isostearate, hexyl laurate, PPG-2 methyl glucose etherdistearate, PEG-100 stearate, and mixtures thereof.

Another group of non-ionic surfactants useful herein are fatty acidester blends based on a mixture of sorbitan or sorbitol fatty acid esterand sucrose fatty acid ester, the fatty acid in each instance beingpreferably C8-C24, more preferably C10-C20. The preferred fatty acidester emulsifier is a blend of sorbitan or sorbitol C16-C20 fatty acidester with sucrose C10-C16 fatty acid ester, especially sorbitanstearate and sucrose cocoate. This is commercially available from ICIunder the tradename Arlatone 2121.

Other suitable surfactants useful herein include a wide variety ofcationic, anionic, zwitterionic, and amphoteric surfactants such as areknown in the art and discussed more fully below. The hydrophilicsurfactants useful herein can contain a single surfactant, or anycombination of suitable surfactants. The exact surfactant (orsurfactants) chosen will depend upon the pH of the composition and theother components present.

Also useful herein are cationic surfactants, especially dialkylquaternary ammonium compounds, examples of which are described in U.S.Pat. No. 5,151,209; U.S. Pat. No. 5,151,210; U.S. Pat. No. 5,120,532;U.S. Pat. No. 4,387,090; U.S. Pat. No. 3,155,591; U.S. Pat. No.3,929,678; U.S. Pat. No. 3,959,461; McCutcheon's, Detergents &Emulsifiers, (North American edition 1979) M.C. Publishing Co.; andSchwartz, et al., Surface Active Agents, Their Chemistry and Technology,New York: Interscience Publishers, 1949. Nonlimiting examples of thesecationic emulsifiers include cetearyl olivate, sorbitan olivate,stearamidopropyl PG-dimonium chloride phosphate, behenamidopropyl PGdimonium chloride, stearamidopropyl ethyldimonium ethosulfate,stearamidopropyl dimethyl (myristyl acetate) ammonium chloride,stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyldimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate,and mixtures thereof. Especially preferred is behenamidopropyl PGdimonium chloride.

Nonlimiting examples of quaternary ammonium salt cationic surfactantsinclude those selected from cetyl ammonium chloride, cetyl ammoniumbromide, lauryl ammonium chloride, lauryl ammonium bromide, stearylammonium chloride, stearyl ammonium bromide, cetyl dimethyl ammoniumchloride, cetyl dimethyl ammonium bromide, lauryl dimethyl ammoniumchloride, lauryl dimethyl ammonium bromide, stearyl dimethyl ammoniumchloride, stearyl dimethyl ammonium bromide, cetyl trimethyl ammoniumchloride, cetyl trimethyl ammonium bromide, lauryl trimethyl ammoniumchloride, lauryl trimethyl ammonium bromide, stearyl trimethyl ammoniumchloride, stearyl trimethyl ammonium bromide, lauryl dimethyl ammoniumchloride, stearyl dimethyl cetyl ditallow dimethyl ammonium chloride,dicetyl ammonium chloride, dicetyl ammonium bromide, dilauryl ammoniumchloride, dilauryl ammonium bromide, distearyl ammonium chloride,distearyl ammonium bromide, dicetyl methyl ammonium chloride, dicetylmethyl ammonium bromide, dilauryl methyl ammonium chloride, dilaurylmethyl ammonium bromide, distearyl methyl ammonium chloride, distearylmethyl ammonium bromide, and mixtures thereof. Additional quaternaryammonium salts include those wherein the C12 to C30 alkyl carbon chainis derived from a tallow fatty acid or from a coconut fatty acid. Theterm “tallow” refers to an alkyl group derived from tallow fatty acids(usually hydrogenated tallow fatty acids), which generally have mixturesof alkyl chains in the C16 to C18 range. The term “coconut” refers to analkyl group derived from a coconut fatty acid, which generally havemixtures of alkyl chains in the C12 to C14 range. Examples of quaternaryammonium salts derived from these tallow and coconut sources includeditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methylsulfate, di(hydrogenated tallow) dimethyl ammonium chloride,di(hydrogenated tallow) dimethyl ammonium acetate, ditallow dipropylammonium phosphate, ditallow dimethyl ammonium nitrate,di(coconutalkyl)dimethyl ammonium chloride, di(coconutalkyl)dimethylammonium bromide, tallow ammonium chloride, coconut ammonium chloride,and mixtures thereof. An example of a quaternary ammonium compoundhaving an alkyl group with an ester linkage is ditallowyl oxyethyldimethyl ammonium chloride.

More preferred cationic surfactants are those selected frombehenamidopropyl PG dimonium chloride, dilauryl dimethyl ammoniumchloride, distearyl dimethyl ammonium chloride, dimyristyl dimethylammonium chloride, dipalmityl dimethyl ammonium chloride, distearyldimethyl ammonium chloride, stearamidopropyl PG-dimonium chloridephosphate, stearamidopropyl ethyldiammonium ethosulfate,stearamidopropyl dimethyl (myristyl acetate) ammonium chloride,stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyldimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate,and mixtures thereof.

Still more preferred cationic surfactants are those selected frombehenamidopropyl PG dimonium chloride, dilauryl dimethyl ammoniumchloride, distearyl dimethyl ammonium chloride, dimyristyl dimethylammonium chloride, dipalmityl dimethyl ammonium chloride, and mixturesthereof.

A preferred combination of cationic surfactant and structuring agent isbehenamidopropyl PG dimonium chloride and/or behenyl alcohol, whereinthe ratio is preferably optimized to maintain to enhance physical andchemical stability, especially when such a combination contains ionicand/or highly polar solvents.

A wide variety of anionic surfactants can also be useful herein.Nonlimiting examples of anionic surfactants include the alkoylisethionates, and the alkyl and alkyl ether sulfates. The reactionproducts of fatty acids esterified with isethianonic acid andneutralized, i.e. the alkoyl isethionates typically have the formulaRCO—OCH₂CH₂SO₃M wherein R is alkyl or alkenyl of from about 10 to about30 carbon atoms, and M is a water-soluble cation such as ammonium,sodium, potassium and triethanolamine. For example, the fatty acids arederivated from coconut or palm kernel oil. Nonlimiting examples of theseisethionates include those alkoyl isethionates selected from ammoniumcocoyl isethionate, sodium cocoyl isethionate, sodium lauroylisethionate, sodium stearoyl isethionate, and mixtures thereof. Alsosuitable are salts of fatty acids, amids of methyl taurides. Othersimilar anionic surfactants are described in U.S. Pat. Nos. 2,486,921;2,486,922 and 2,396,278.

The alkyl and alkyl ether sulfates typically have the respectiveformulae ROSO₃M and RO(C₂H₄O)xSO₃M, wherein R is alkyl or alkenyl offrom about 10 to about 30 carbon atoms, x is from about 1 to about 10,and M is a water-soluble cation such as ammonium, alkanolamines such astriethanolamine, monovalent metals, such as sodium and potassium, andpolyvalent metal cations such as magnesium and calcium. Preferably, Rhas from about 8 to about 18 carbon atoms, more preferably from about 10to about 16 carbon atoms, even more preferably from about 12 to about 14carbon atoms, in both the alkyl and alkyl ether sulfates. The alkylether sulfates are typically made as condensation products of ethyleneoxide and monohydric alcohols having from about 8 to about 24 carbonatoms. The alcohols can be synthetic or they can be derived from fats,e.g., coconut oil, palm kernel oil, tallow. Lauryl alcohol and straightchain alcohols derived from coconut oil or palm kernel oil arepreferred. Such alcohols are reacted with between about 0 and about 10,preferably from about 2 to about 5, more preferably about 3, molarproportions of ethylene oxide, and the resulting mixture of molecularspecies having, for example, an average of 3 moles of ethylene oxide permole of alcohol, is sulfated and neutralized

Another suitable class of anionic surfactants are the water-solublesalts of the organic, sulfuric acid reaction products of the generalformula: R1-SO₃-M wherein R1 is chosen from the group including astraight or branched chain, saturated aliphatic hydrocarbon radicalhaving from about 8 to about 24, preferably about 10 to about 16, carbonatoms; and M is a cation described hereinbefore. Still other anionicsynthetic surfactants include the class designated as succinamates,olefin sulfonates having about 12 to about 24 carbon atoms, andβ-alkyloxy alkane sulfonates. Examples of these materials are sodiumlauryl sulfate and ammonium lauryl sulfate. Other anionic surfactantssuitable for use in the compositions are the succinnates, examples ofwhich include disodium N-octadecylsulfosuccinnate; disodium laurylsulfosuccinate; diammonium lauryl sulfosuccinate; tetrasodiumN-(1,2-dicarboxyethyl)-N-octadecylsulfosuccinnate; diamyl ester ofsodium sulfosuccinic acid; dihexyl ester of sodium sulfosuccinic acid;and dioctyl esters of sodium sulfosuccinic acid. Other suitable anionicsurfactants include olefin sulfonates having about 10 to about 24 carbonatoms. In addition to the true alkene sulfonates and a proportion ofhydroxy-alkanesulfonates, the olefin sulfonates can contain minoramounts of other materials, such as alkene disulfonates depending uponthe reaction conditions, proportion of reactants, the nature of thestarting olefins and impurities in the olefin stock and side reactionsduring the sulfonation process. A non limiting example of such analpha-olefin sulfonate mixture is described in U.S. Pat. No. 3,332,880.

Another class of anionic surfactants suitable for use in thecompositions are the beta-alkyloxy alkane sulfonates. These surfactantsconform to the formula

where R1 is a straight chain alkyl group having from about 6 to about 20carbon atoms, R2 is a lower alkyl group having from about 1 to about 3carbon atoms, preferably 1 carbon atom, and M is a water-soluble cationas described hereinbefore. Other anionic materials useful herein aresoaps (i.e. alkali metal salts, e.g., sodium or potassium salts) offatty acids, typically having from about 8 to about 24 carbon atoms,preferably from about 10 to about 20 carbon atoms. The fatty acids usedin making the soaps can be obtained from natural sources such as, forinstance, plant or animal-derived glycerides (e.g., palm oil, coconutoil, soybean oil, castor oil, tallow, lard, etc.) The fatty acids canalso be synthetically prepared. Soaps are described in more detail inU.S. Pat. No. 4,557,853. Amphoteric and zwitterionic surfactants arealso useful herein. Examples of amphoteric and zwitterionic surfactantswhich can be used in the compositions of the present invention are thosewhich are broadly described as derivatives of aliphatic secondary andtertiary amines in which the aliphatic radical can be straight orbranched chain and wherein one of the aliphatic substituents containsfrom about 8 to about 22 carbon atoms (preferably C8-C18) and onecontains an anionic water solubilizing group, e.g., carboxy, sulfonate,sulfate, phosphate, or phosphonate. Examples are alkyl imino acetates,and iminodialkanoates and aminoalkanoates of the formulas RN[CH₂)mCO₂M]₂and RNH(CH₂)mCO₂M wherein m is from 1 to 4, R is a C8-C22 alkyl oralkenyl, and M is H, alkali metal, alkaline earth metal ammonium, oralkanolammonium. Preferred amphoteric surfactants for use in the presentinvention include cocoamphoacetate, cocoamphodiacetate,lauroamphoacetate, lauroamphodiacetate, and mixtures thereof. Alsoincluded are imidazolinium and ammonium derivatives. Specific examplesof suitable amphoteric surfactants include sodium3-dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate,N-alkyltaurines such as the one prepared by reacting dodecylamine withsodium isethionate according to the teaching of U.S. Pat. No. 2,658,072;N-higher alkyl aspartic acids such as those produced according to theteaching of U.S. Pat. No. 2,438,091; and the products sold under thetradename “Miranol” and described in U.S. Pat. No. 2,528,378. Otherexamples of useful amphoterics include phosphates, such as coamidopropylPG-dimonium chloride phosphate (commercially available as Monaquat PTC,from Mona Corp.).

Zwitterionic surfactants suitable for use in the composition are wellknown in the art, and include those surfactants broadly described asderivatives of aliphatic quaternary ammonium, phosphonium, and sulfoniumcompounds, in which the aliphatic radicals can be straight or branchedchain, and wherein one of the aliphatic substituents contains from about8 to about 18 carbon atoms and one contains an anionic group such ascarboxy, sulfonate, sulfate, phosphate or phosphonate. Zwitterionicssuch as betaines are preferred. Examples of betaines include the higheralkyl betaines, such as coco dimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethylbetaine, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl betaine(available as Lonzaine 16SP from Lonza Corp.), laurylbis-(2-hydroxyethyl) carboxymethyl betaine, stearylbis-(2-hydroxypropyl) carboxymethyl betaine, oleyl dimethylgamma-carboxypropyl betaine, laurylbis-(2-hydroxypropyl)alpha-carboxyethyl betaine, coco dimethylsulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryldimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl) sulfopropylbetaine, and amidobetaines and amidosulfobetaines (wherein theRCONH(CH₂)₃ radical is attached to the nitrogen atom of the betaine),oleyl betaine (available as amphoteric Velvetex OLB-50 from Henkel), andcocamidopropyl betaine (available as Velvetex BK-35 and BA-35 fromHenkel).

Other useful amphoteric and zwitterionic surfactants include thesultaines and hydroxysultaines such as cocamidopropyl hydroxysultaine(available as Mirataine CBS from Rhone-Poulenc), and the alkanoylsarcosinates corresponding to the formula RCON(CH₃)CH₂CH₂CO₂M wherein Ris alkyl or alkenyl of about 10 to about 20 carbon atoms, and M is awater-soluble cation such as ammonium, sodium, potassium andtrialkanolamine (e.g., triethanolamine), a preferred example of which issodium lauroyl sarcosinate.

c. Water Emollient

The preferred oil-in-water emulsion contains from about 25% to about98%, preferably from about 65% to about 95%, more preferably from about70% to about 90% water by weight of the topical carrier.

The hydrophobic phase is dispersed in the continuous aqueous phase. Thehydrophobic phase may contain water insoluble or partially solublematerials such as are known in the art, including but not limited to thesilicones described herein in reference to silicone-in-water emulsions,and other oils and lipids such as described above in reference toemulsions.

The topical compositions of the subject invention, including but notlimited to lotions and creams, may contain a dermatologically acceptableemollient. Such compositions preferably contain from about 1% to about50% of the emollient. As used herein, “emollient” refers to a materialuseful for the prevention or relief of dryness, as well as for theprotection of the skin. A wide variety of suitable emollients is knownand may be used herein. Sagarin, Cosmetics, Science and Technology, 2ndEdition, Vol. 1, pp. 32-43 (1972) contains numerous examples ofmaterials suitable as an emollient. A preferred emollient is glycerin.Glycerin is preferably used in an amount of from about 0.001 to about30%, more preferably from about 0.01 to about 20%, still more preferablyfrom about 0.1 to about 10%, e.g., 5%.

Lotions and creams according to the present invention generally containa solution carrier system and one or more emollients. Lotions and creamstypically contain from about 1% to about 50%, preferably from about 1%to about 20%, of emollient; from about 50% to about 90%, preferably fromabout 60% to about 80%, water; the polypeptides, according to theinvention, and the additional skin care active (or actives) in the abovedescribed amounts. Creams are generally thicker than lotions due tohigher levels of emollients or higher levels of thickeners.

Ointments of the present invention may contain a simple carrier base ofanimal or vegetable oils or semi-solid hydrocarbons (oleaginous);absorption ointment bases which absorb water to form emulsions; or watersoluble carriers, e.g., a water soluble solution carrier. Ointments mayfurther contain a thickening agent, such as described in Sagarin,Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 72-73(1972), and/or an emollient. For example, an ointment may contain fromabout 2% to about 10% of an emollient; from about 0.1% to about 2% of athickening agent; and the polypeptide and the additional skin careactive (or actives) in the above described amounts.

Compositions of this invention useful for cleansing (“cleansers”) can beformulated with a suitable carrier, e.g., as described above, andpreferably comprise from about 1% to about 90%, more preferably fromabout 5% to about 10%, of a dermatologically acceptable surfactant. Thesurfactant is suitably selected from anionic, nonionic, zwitterionic,amphoteric and ampholytic surfactants, as well as mixtures of thesesurfactants. Such surfactants are well known to those skilled in thedetergency art. Nonlimiting examples of possible surfactants includeisoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyltaurate, and sodium lauryl sulfate. See U.S. Pat. No. 4,800,197 forexemplary surfactants useful herein. Examples of a broad variety ofadditional surfactants useful herein are described in McCutcheon'sDetergents and Emulsifiers, North American Edition (1986), published byAllured Publishing Corporation. The cleansing compositions canoptionally contain, at their art-established levels, other materialswhich are conventionally used in cleansing compositions.

As used herein, the term “foundation” refers to a liquid, semi-liquid,semi-solid, or solid skin cosmetic which includes, but is not limited tolotions, creams, gels, pastes, cakes, and the like. Typically thefoundation is used over a large area of the skin, such as over the face,to provide a particular look. Foundations are typically used to providean adherent base for color cosmetics such as rouge, blusher, powder andthe like, and tend to hide skin imperfections and impart a smooth, evenappearance to the skin. Foundations of the present invention include adermatologically acceptable carrier and may include conventionalingredients such as oils, colorants, pigments, emollients, fragrances,waxes, stabilizers, and the like. Exemplary carriers and such otheringredients which are suitable for use herein are described, forexample, in WO96/33689, and GB 2274585.

B. Orally Acceptable Carrier

The compositions of the present invention can also comprise an orallyacceptable carrier if they are to be ingested. Any suitable orallyingestible carrier or carrier form, as known in the art or otherwise,can be used. Non-limiting examples of oral personal care compositionscan include, but are not limited to, tablets, pills, capsules, drinks,beverages, syrups, granules, powders, vitamins, supplements, healthbars, candies, chews, and drops.

C. Injectible Liquid

The compositions of the present invention can also comprise a liquidthat is acceptable for injection in and/or under the skin if thecomposition is to be injected. Any suitable acceptable liquid as knownin the art or otherwise can be used.

III COMPOSITION PREPARATIONS

The compositions useful for the methods of the present invention aregenerally prepared by conventional methods such as are known in the artof making topical and oral compositions and compositions for injection.Such methods typically can involve mixing of the ingredients in one ormore steps to a relatively uniform state, with or without heating,cooling, application of vacuum, and the like.

The physical form of the compositions according to the invention is notimportant: creams, lotions, ointments, milks, gels, emulsions,dispersions, solutions, suspensions, cleansers, foundations, anhydrouspreparations (sticks, in particular lipsticks, body and bath oils),shower and bath gels, shampoos and scalp treatment lotions, cream orlotion for care of the skin or hair, sun-screen lotions, milks orcreams, artificial suntan lotions, creams or milks, shaving creams orfoams, aftershave lotions, make-up, mascaras or nail varnishes,lipsticks, skin “essences,” serums, adhesive or absorbent materials,transdermal patches, powders, emollient lotion, emollient milk,emollient cream, sprays, oils for the body and the bath, foundation tintbases, pomade, emulsion, colloid, compact or solid suspension, pencil,sprayable formulation, brossable, rouge, blush, eyeliner, lipliner, lipgloss, facial or body powder, mousse, styling gels, nail conditioner,brush on formulation, lip balms, skin conditioners, cold creams,moisturizers, hair sprays, soaps, body scrubs, exfoliants, astringents,depilatories and permanent waving solutions, antidandruff formulations,anti-sweat and antiperspirant compositions, shaving, pre-shaving andafter-shaving products, moisturizers, deodorants, cold creams,cleansers, skin gels, rinses, nose sprays and so on. These compositionscan also be presented in the form of lipsticks intended to apply colouror to protect the lips from cracking, or of make-up products for theeyes or tints and tint bases for the face. Compositions in accordancewith the invention include cosmetics, personal care products andpharmaceutical preparations. One can also consider a composition in theshape of foam or in the form of compositions for aerosol also includinga propellant agent under pressure.

Cosmetic compositions may also be for orodental use, for example,toothpaste. In that case, the compositions may contain the usualadjuvants and additives for compositions for oral use and, inparticular, surfactants, thickening agents, moisturizing agents,polishing agents such as silica, various active substances such asfluorides, particularly sodium fluoride, and, possibly, sweeteningagents such as saccharin sodium.

The compositions according to the present invention may be in the formof solution, dispersion, emulsion, paste, or powder. They may beincluded individually or as a premix in vehicles such as macro-, micro-,or nanocapsules, macro-, micro- or, nanospheres, liposomes, oleosomes orchylomicrons, macro-, micro-, or nanoparticles or macro-, micro ornanosponges. They may also be adsorbed on organic polymer powders,talcs, bentonites, or other inorganic or organic supports.

Peptides comprising at least one immobilized aromatic cycle andcorresponding to general formula (I), and composition according to theinvention may be used in any form whatsoever, or in a form bound to orincorporated in or absorbed in or adsorbed on macro-, micro-, andnanoparticles, or macro-, micro-, and nanocapsules, for the treatment oftextiles, natural or synthetic fibres, wools, and any materials that maybe used for clothing or underwear for day or night intended to come intocontact with the skin, such as tights, underclothes, handkerchiefs,wipes or cloths, to exert their cosmetic effect via this skin/textilecontact and to permit continuous topical delivery.

IV METHODS FOR COSMETIC TREATMENT

The composition according to the invention can be locally applied on theparts of the face or of the body to lighten. One of the advantages ofthe present invention is the possibility of being available to proceed,each time it is necessary or desirable, to “soft” treatments verylocalized and selective thanks to the application way by topical route.

The present invention also concerns a method of decreasing skinpigmentation, whitening or bleaching human skin, lightening skincomplexion or any pigmentation associated with melanin, homogenizingskin color, preventing or reducing melanogenesis, reducing coloration onexposure to natural or artificial UV radiation, attenuating senile spotssuch as senile lentigo, treating or preventing cutaneoushyperpigmentation and/or melasma and/or chloasma, and/or freckles and/orliver spots comprising applying to the skin in need a such treatment, asafe and effective amount of at least on peptide comprising at least oneimmobilized aromatic cycle and correspond to general formula (I) or acomposition according to the present invention.

The present invention also relates a method of reducing at least onesign of aging such as undesired pigmentation for example localhyperpigmentation and incorrect pigmentation (for example liver spots,senile lentigo, freckles), comprising applying to a portion of humanskin showing signs of aging, a safe and effective amount of at least onpeptide comprising at least one immobilized aromatic cycle andcorrespond to general formula (I) or a composition according to thepresent invention, at least once a day for a period of time at leastsufficient to provide a reduction in the visible signs of aging.

Another object of the present invention is the use of at least one ofsaid peptide containing at least one immobilized aromatic cycleaccording to general formula (I), to manufacture a medicament regulatingprophylacticly and therapeutically the unwanted pigmentation, such ashyperpigmentation.

The decreasing pigmentation, the whitening effect, the unifying of thecomplexion, the prevention and/or treatment of the signs of cutaneousaging, the protection and/or improvement of the state of the skin andthe prevention and/or treatment of skin imperfections arecharacteristics of a functional nature that can be analyzed, measuredand quantified using numerous techniques known by cosmetic treatmentprofessionals.

Thus variation of uniformity of the complexion, variation inpigmentation (hypo- and hyper-pigmentation), erythrosis, localizederythema, variation in the clarity and luminosity of the complexion,pigmented lentigines and dullness can be measured using the Mexameter®or Chromameter®.

The Visia® system enables quantification of senile lentigines visibleunder UV light, porphyrins, and variations in pore size under visiblelight.

Wrinkles and fine lines can be quantified, in particular, by the methodconsisting in taking silicone replica that can be analyzed using acamera and image analysis system or using the Visia®. Cutaneoushydration is determined, in particular, by Corneometer®, the D-Squame®stripping method or the trans-epidermal water loss (TEWL) method. TheTEWL, which enables quantitation of the impairment of cutaneous barrierproperties, can be determined using the Delfin Vapometer®. The decreasein sebum secretion may be studied using Sebutape® or the Sebumeter®. Theloss of firmness and/or elasticity and/or tone and skin fatigue may bequantified using the Cutometer®. Thinning of the skin may be determinedusing ultrasound, MRI and confocal microscopy while atrophy of theepidermis may be measured using the microdepression network (MDN). Thelatter technique also enables investigation of the anisotropiccharacteristics of the skin. The roughness of the skin and the variationin its grain may be measured, in particular, by the method consisting intaking silicone replica that can be analyzed using a camera and imageanalysis software. The decrease in the softness of the skin may bemeasured using a Frictiometer®. The decrease in cutaneousmicrocirculation may be analyzed using laser Doppler flowmetry orcapillaroscopy. The change in cutaneous pH may be quantified using apH-meter. D-Squame® stripping enables collection of stratum corneumspecimens and evaluation of the surface by image analysis.

The variation of melanogenesis and the variation of synthesizedmolecules of the extracellular matrix of the dermis and epidermis canmeasured and quantified using numerous in vitro techniques known tocosmetic treatment professionals. For example, the efficacy of theproducts on melanization can be tested on cultured pigmented cells,melanocytes or on stable cell line, such as melanocytes of line B16, thetotal melanin present in the cells being determined after cell lysis andthe assay being colorimetric. It is also possible to quantify theinhibition of tyrosinase activity with a DOPA method.

Moreover, it is possible to quantify the synthesis of various collagen,for example I, III, and IV, to quantify the synthesis of elastin,fibronectin, hyaluronic acid or lamimin thanks to cultured fibroblastsand to quantify the synthesis of molecules related to keratinocytesdifferentiation (such as in, filaggrin, keratine 10, transglutaminase,loricrin)

INDUSTRIAL APPLICABILITY

The present invention relates to the chemical, medical, cosmetic andpersonal care industries.

V EXAMPLES

The following examples further describe and demonstrate embodimentswithin the scope of the present invention. The examples are given solelyfor the purpose of illustration and are not to be construed aslimitations of the present invention, as many variations thereof arepossible without departing from the spirit and scope of the invention.As an illustration of the invention, several cosmetic formulae will becited. The formulae are representative of, but do not restrict, theinvention.

A. Formula Examples 1) Lightening Gel

PRODUCT % Part A Ultrez 10 [Carbomer] 0.20 Water deionised qsp 100Part B Glycerin 5.00 Methyl paraben 0.20 Part C Hydroxyethyl Cellulose0.20 Part D Palmitoyl-Tyr-Gly-Gly-Phe-Pro 0.01 (SEQ ID NO 2)Ascorbyl phosphate 0.01 Crillet 1 [Polysorbate 20] 0.50 Part EPemulen TR2 [Acrylates/C 10—30 0.20 Alkyl Acrylate Cross Polymer]DC 200 [Dimethicone] 2.00 Part F Potassium Sorbate 0.10 Part GWater deionised 4.00 Sodium Hydroxide 30% 0.40 Part H Fragrance 0.10

Method: Part A: sprinkle Ultrez 10 in the water and allow to swell for15 minutes. Melt Part B to 60° C. and allow to cool to around 40° C. MixPart C with Part B, homogenize. Add Part B+C to Part A with helixstirring and allow to swell for 1 hour. Heat Part D to 80° C. Heat PartA+B+C to 80° C. Pour Part D into Part A+B+C with Staro stirring (3000rpm). Mix part E and, extemporaneously, add it to the previous part.Then add part F at 75° C. and allow to swell for 1 hour. Neutralize withPart G at 50° C. Add Part H at 35° C. Mix well.

2) Whitening Soothing Day Cream

PRODUCT % Water Deionised qs 100 Ultrez 10 [Carbomer] 0.20 Part BPotassium Sorbate 0.10 Part C Butylene Glycol 2.00Phenova [Phenoxyethanol (and) Mixed 0.80 Parabens] Part DCrill 3 [Sorbitan Stearate] 1.00 Crillet 3 [Polysorbate 60] 2.50DC 200 [Dimethicone] 2.50 Crodamol TN [Isotridetyl Isononanoate] 5.00Crodamol GTCC [Caprylic/Capric 5.00 Triglyceride]Crodamol SS [Cetyl Esters] 1.00 Super Hartolan [Lanolin Alcohol] 0.50Super Sterol Ester [C10—C30 Cholesterol/ 0.30 Lanosterol esters]Crodacol CS90 [Cetearyl Alcohol] 3.00 Part E Water Deionised 2.50Sodium Hydroxide 38% 0.25 Part F H-Tpi-Ile-OH 0.002 (SEQ ID NO 14)CALMOSENSINE ® 4.00 Part G Liquorice extract 3.00

Calmosensine® is an analgesic peptide offered by SEDERMA (WO98/07744).Method: Part A: disperse Ultrez 10 in water and let it swell for 20minutes, then add Part B; heat to 75° C. Heat Part C separately to 75°C. Mix the two Parts under stirring, homogenise, add Part D, neutralisewith Part E, cool until reaching 30° C., then add Part F and Part G,adjust pH to ˜6 with NaOH.

3) Moisturizing and Anti-Wrinkle Foundation

Compounds % (w/w) Phase A Water Deionised 53.36 KOH 10% 1.30Polysorbate 80 0.10 Phase B Titanium dioxyde 6.00 Talc 3.05Yellow Iron Oxide 1.80 Red Iron Oxide 1.00 Black Iron Oxide 0.15 Phase CPropylene glycol 6.00 Magnesium Aluminium Silicate 1.00 Phase DPropylene glycol 2.00 Sodium Carboxymethyl- 0.12 cellulose Phase EDiPPG3 Myristyl Ether Adipate 12.00 Isostearyl Neopentanoate 4.00Crodafos CS 20 4.00 Steareth-10 2.00 Cetyl Alcohol 0.50 Steareth-2 0.50Ceramide 2 0.10 Matrixyl3000 ® 3.00 Pal-Tic-NH₂ 0.002 (SEQ ID NO 9)Pal-His-Leu-Asp-Ile-Ile-Phe 0.0001 (SEQ ID NO 29) Pal-Ile-D-Tic-Ala0.0004 Preservatives qsp 100

Method: Phase A: disperse Ultrez 10 in water and let it swell for 20minutes, Mix pigments then add phase B into Phase A; heat. Heat Phase Cseparately. Mix the two phases under stirring, homogenise, add Phase D,prepare phase E, Add phase E into (A+B+C+D) under stirring. adjust pH to˜7.5 with NaOH.

4) Face Lotion

Compounds % (w/w) Ultrez 10 0.30 Butylene Glycol 5.00 Mixed Parabens0.20 Crodamol ICS 1.00 Crodamol AB 4.00 Pemulen TR2 0.25 Crillet 1 1.00Potassium Sorbate 0.10 Sodium hydroxide 10N 0.55 VENUCEANE ™ 5.00Ac-7-OH-Tic-Gly-Gly-Phe-Leu-OH 0.002 (SEQ ID NO 4)Biot-Tyr-Gly-Gly-Phe-Leu 0.03 (SEQ ID NO 48) Pal-His-Leu-Asp-Ile-Tpi-Ile0.002 (SEQ ID NO 27) Fragrance 0.10 Water Deionised qsp 100

5) Anti-Wrinkle Cream for Mature Skin

Compounds % (w/w) Phase A Ultrez 10 0.20 Water Deionised qsp 100 Phase BGlycerin 3.50 Phase C Potassium Sorbate 0.10 Volpo S10 1.50 Crodafos CES3.50 DC 2002.00 Crodamol OSU 7.00 Vitamin C 0.10 Crill 3 0.40Sodium Hydroxide 30% 0.20 STEROCARE ™ 3.00 Ac-Tic(OH)-Gly 0.002(SEQ ID NO 21) Pal-D-7-hydroxy-Tic 3.00 Ac-Tic-Gly-Gly-Phe-Leu-OH 0.002(SEQ ID NO 20) Water, preservatives, fragrance qsp 100

6) Moisturizing and Lightening Body Milk

Compounds % (w/w) Crillet 3 2.5 Novol 0.9 Fluilan 2.5 Carbopol 940 0.3Beeswax 2.0 NaOH 30% 0.1 Glycerine 5.0 Pal-Tyr-Gly-Gly-Phe-Leu-OH 0.01(SEQ ID NO 1) Ac-Tic-Gly-OH 0.002 (SEQ ID NO 13) H-Ile-Tpi-Lys-OH 0.003(SEQ ID NO 19) Water & preservatives qs 100 g

7) Day Cream

Compounds % (w/w) Volpo S20 2.4 Volpo S2 2.6 Prostearyl 15 8.0 Beeswax0.5 Stearoxy dimethicone 3.0 Propylene glycol 3.0 Carbomer 0.25 NaOH 30%0.25 Ac-Tic-Leu-Asp-Ile-Ile-Trp-OH 0.01 (SEQ ID NO 7) H-Tpi-Ala-OH 0.002(SEQ ID NO 15) Pal-Tpi-NH2 0.003 (SEQ ID NO 23) Water & preservativesqs 100 g

8) Anti-Wrinkle Night Cream

Compounds % (w/w) PART A H2O 70.95 Ultrez 10 [Carbomer] 0.15 PART BGlycerin [Glycerin] 3.50 PART C Volpo S 2 [Steareth 2] 0.40Crodafos CES [Cetearyl alcohol dicetyl 4.00phosphate & ceteth 10 phosphate] DC 345 [Cyclohexasiloxane] 2.00Crodamol OSU [Dioctyl succinate] 7.00 Volpo S 10 [Steareth 10] 1.20Nipastat [Mixed parabens] 0.30 PART D Sorbate [Sorbate] 0.10 PART E H2O2.50 NaOH 38% [Sodium hydroxide] 0.30 PART F Perfume [Fragrance] 0.10PART G MATRIXYL3000 ® 3.00 Pal-Tyr-Gly-Gly-Tic-Leu-OH 0.002(SEQ ID NO 3) H-Tpi-Lys-OH 0.002 (SEQ ID NO 16)Ac-Phe-Leu-Asp-Ile-Ile-Trp 0.002 (SEQ ID NO 30)

MATRIXYL 3000® is sold by SEDERMA, The resulting emulsion should be wellsuited for fragile, aged skin, to improve fine lines, wrinkles, anddryness, reduce redness and irritation.

Method: PART A: disperse Ultrez 10 in water and let it swell for 20minutes, then add PART B; heat to 75° C. Heat PART C separately to 75°C. Mix the two phases under stirring, homogenise, add PART D, neutralisewith PART E, cool until reaching 30° C., then add PART F and PART G,adjust pH to 6 with NaOH.

9) Moisturizing Face Gel

Compounds % (w/w) PART A Ultrez 10 [Carbomer] 0.20 Water Deionisedqs 100 PART B Glycerin 3.00 Phenova [Phenoxyethanol (and) Mixed 0.80Parabens] PART C Crillet 1 [Polysorbate 20] 0.50 PART DPotassium Sorbate 0.10 PART E Pemulen TR1 [Acrylates/C10-30 Alkyl 0.20Acrylate Crosspolymer] DC 345 [Cyclomethicone] 3.00 PART F Water 4.00Sodium Hydroxide 38% 0.40 PART G MOIST-24 ® 5.00Ste-Tyr-Gly-Gly-Tpi-Leu-OH 0.002 (SEQ ID NO 5) Pal-Tic-Leu 0.002(SEQ ID NO 22) H-Tpi-Phe-OH 0.003 (SEQ ID NO 17)

MOIST-24® is a moisturizing plant extract (Imperata Cylindrica (root)sold by SEDERMA (WO 01/62218 of Aug. 30, 2001).

Method: PART A disperse Ultrez 10 in water and let it swell for 20minutes, then add PART B; heat to 75° C. Heat PART C separately to 75°C. Mix the two phases under stirring, homogenise, add PART D, neutralisewith PART E, cool until reaching 30° C., then add PART F and PART G,adjust pH to −6 with NaOH.

10) Lotion to Treat Dark Circles Under the Eyes

Compounds % (w/w) PART A Ultrez 10 [Carbomer] 0.20 Water Deionisedqs 100 PART B Glycerin 3.00 PART C Potassium Sorbate 0.10 PART DVolpo S10 [Steareth 10] 1.50 Crodafos CES [Ceterayl Alcohol Dicetyl 3.00Phosphate (and) Ceteth-10 Phosphate] DC 200 [Dimethicone] 2.00Crodamol OSU [Diethylhexyl Succinate] 5.00 Mixed Parabens 0.30Crill 3 [Sorbitan Stearate] 0.40 PART E Sodium Hydroxide 38% 0.20Water Deionised 4.00 PART F Water 10.0 Pal-Gly-His-Lys 0.0005Ste-Tpi-Ile 0.00025 (SEQ ID NO 26) H-Tpi-Gly-OH 0.00025 (SEQ ID NO 18)Ste-Tyr-Gly-Gly-Trp-Leu 0.002 (SEQ ID NO 31) Deferoxamine 0.001Berberine 0.002

Method: PART A disperse Ultrez 10 in water and let it swell for 20minutes, then add PART B; heat to 75[deg.] C. Heat PART C separately to75[deg.] C. Mix the two phases under stirring, homogenize, add PART D,neutralize with PART E, cool until reaching 30[deg.] C., then add PART Fand PART G, adjust pH to −6 with NaOH.

B. Preparation of Peptides According to the Invention

These compounds have been synthesized on resin Rink amide PS or on resinWang PS using the standard synthesis strategy in solid phase Fmoc(9-fluorenyl-methoxycarbonyle). These resins were purchased from SennChemicals.

Chemical products used are the following: amino acids protected atN-terminal extremity by a group Fmoc, Fmoc-Ala-OH, Fmoc-D-Ala-OH,Fmoc-Arg(Pbf)-OH, Fmoc-D-Arg(Pbf)-OH, Fmoc-His(Trt)-OH,Fmoc-D-His(Trt)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Phe-OH, Fmoc-D-Phe-OH,FmocTrp(Boc)-OH, Fmoc-D-Trp(Boc)-OH, Fmoc-Met-OH, Fmoc-Glu(OtBu)-OH,FmocSer(tBu)-OH, Fmoc-Leu-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Gly-OH,Fmoc-Pro-OH, Fmoc-Asn(trt)-OH, were purchased from SENN chemicals andfrom Advanced Chemte.

The N,N-dimethylformamide (DMF), the dichloromethane, methanol, theacetonitrile, ethylic ether, trifluoracetic acid (TFA), the piperidine,were purchased from Riedel-de Haên, Carlo Erba or Acros Organics andused without purification.

The N,N-diisopropylethylamine (DIEA), the diisopropylcarbodiimide (DIC),the N-hydroxybenzotriazole (HOBt), the triisopropylsilane, the palmiticacid were purchased from SAF or Avocado. All the reactants and chemicalproducts were from analytical quality and were used without anypurification.

The standard manufacturing process of these peptides comprises thefollowing phases:

1) Standard Protocol for Fmoc Deprotection

The Fmoc deprotection phases were realized by making react the resinsprotected in a mixture of dimethylformamide (DMF)/piperidine (80/20,v/v) during 20 minutes.

2) Standard Protocol for Cleaning

After the coupling or deprotection phase, the cleaning phases wererealized with DMF (3×5 min), methanol (2×5 min) and dichloromethane(DCM) (2×5 min), successively.

3) Standard Protocol for Coupling

A solution containing 2 equivalents of amino acid Fmoc, DIC and HOBt insome DMF is added to the deprotected resin during 2 hours. A ninhydrinetest is realized to evaluate the end of the reaction.

4) Cleavage

The solution TFA/water/triisopropylsilane (95/2.5/2.5, v/v/v) is addedto the resin for cleavage (5 ml/g). The cleavage was realized during 3hours. The resin is filtrated and washed with TFA (5 ml/g). The filtrateis concentrated under vacuum. The compounds are precipitated withdiethylic ether. The samples were solubilised, frozen at −80 C andlyophilized.

The analyses of CLHP were realized on a chromatographic system Agilent1100 with a diode array detector and a C18 Merck Chromolith column of100×4.6 mm thermostated at 35° C. A discharge rate of 1 ml/min and agradient from 20% to 80% of acetonitrile in ammonium formate at 0.1% in20 minutes were used.

1-12. (canceled)
 13. A cosmetic composition comprising: at least onepeptide comprising at least one immobilized aromatic cycle of theformula (I): A-(Xa)m-Xc-(Xb)n-B; wherein A is H, or an N-acyl group,selected from the group consisting of biotin or an alkyl, aryl, aralkyl,acyl, alcohol, sulfonyl, sugar or an alkoxy chain, B is OR¹ or NR²R³, inwhich R¹, R² and R³ are, independently of each other, H or an alkyl,aryl, aralkyl, acyl, alcohol, sulfonyl, sugar or alkoxy chain, “m” and“n” are between 0 and 5 with the proviso that m+n≦5, (Xa) and (Xb) areamino acid residues, which may be the same or different, geneticallyencoded or not encoded, and (Xa)m and (Xb)n are chains from 0 to 5 aminoacids (Xa1, Xa2, Xa3, Xa4, Xa5) (Xb1, Xb2, Xb3, Xb4, Xb5) which may bethe same or different genetically encoded or not encoded, with theproviso that m+n≦5, Xc is an aromatic amino acid, wherein if Xa1=His andn=0, then Xc is an amino acid residue selected from the group consistingof L- or D-Trp, L- or D-Phe, L- or D-Tyr, L- or D-Tic, L- orD-7-hydroxy-Tic, or L- or D-Tpi, and Xa2 is not Ser, Ala, Phe orhomoPhe; if Xa1=L-Tyr, m≦3 and n≦1, then Xc is an amino acid residueselected among L- or D-Trp, L- or D-Phe, L- or D-Tyr, L- or D-Tic, L- orD-7-hydroxy-Tic, or L- or D-Tpi; and if Xa1 is not Tyr and not His,m+n≦5, then Xc is an amino acid residue selected among L- or D-Tic, orL- or D-7-hydroxy-Tic, or L- or D-Tpi.
 14. The cosmetic composition ofclaim 13, wherein if Xa1=His, then Xa2 is Leu.
 15. The cosmeticcomposition of claim 13, wherein the peptide is selected from the groupconsisting of analogs or fragments of enkephalin or endothelin.
 16. Thecosmetic composition of claim 13, wherein the N-acyl group is selectedfrom the group consisting of acetyl, palmitoyl, elaidoyl, myristoyl,biotinyl, and octanoyl.
 17. A cosmetic composition comprising: adermatologically acceptable carrier, and at least one peptide comprisingat least one immobilized aromatic cycle of the formula (I):A-(Xa)m-Xc-(Xb)n-B; wherein A is H, or an N-acyl group, selected fromthe group consisting of biotin or an alkyl, aryl, aralkyl, acyl,alcohol, sulfonyl, sugar or an alkoxy chain, B is OR¹ or NR²R³, in whichR¹, R² and R³ are, independently of each other, H or an alkyl, aryl,aralkyl, acyl, alcohol, sulfonyl, sugar or alkoxy chain, “m” and “n” arebetween 0 and 5 with the proviso that m+n≦5, (Xa) and (Xb) are aminoacid residues, which may be the same or different, genetically encodedor not encoded, and (Xa)m and (Xb)n are chains from 0 to 5 amino acids(Xa1, Xa2, Xa3, Xa4, Xa5) (Xb1, Xb2, Xb3, Xb4, Xb5) which may be thesame or different genetically encoded or not encoded, with the provisothat m+n≦5, Xc is an aromatic amino acid, wherein if Xa1=His and n=0,then Xc is an amino acid residue selected from the group consisting ofL- or D-Trp, L- or D-Phe, L- or D-Tyr, L- or D-Tic, L- orD-7-hydroxy-Tic, or L- or D-Tpi, and Xa2 is not Ser, Ala, Phe orhomoPhe; if Xa1=L-Tyr, m≦3 and n≦1, then Xc is an amino acid residueselected among L- or D-Trp, L- or D-Phe, L- or D-Tyr, L- or D-Tic, L- orD-7-hydroxy-Tic, or L- or D-Tpi; and if Xa1 is not Tyr and not His,m+n≦5, then Xc is an amino acid residue selected among L- or D-Tic, orL- or D-7-hydroxy-Tic, or L- or D-Tpi.
 18. The cosmetic composition ofclaim 17, wherein said peptide is present at a concentration between0.00001% (w/w) and 100% (w/w).
 19. The cosmetic composition of claim 18,wherein said peptide is present at a concentration between 0.0001% (w/w)and 20% (w/w).
 20. The cosmetic composition of claim 19, wherein saidpeptide is present at a concentration between 0.001% and 5% (w/w) byweight of the composition.
 21. The cosmetic composition of claim 17,further comprising at least one skin care active or additionalingredient selected from the group consisting of skin depigmentingagent, skin whitening agent, lightening or bleaching agent, opticalbrightening agent, melanogenesis inhibitor agent, reducing pigmentationagent, keratolytic agent, desquamation agent, skin anti-aging agent,anti-wrinkle agent, anti-atrophy agent, anti-oxidant/radical scavenger,and mixtures thereof.
 22. The cosmetic composition of claim 21, whereinthe skin care active or additional ingredient is selected from the groupconsisting of a tyrosinase inhibitor, protein kinase A or C inhibitor,inhibitor of cellular calcium flux, inhibitor of adrenergic receptors αor β, hydroquinone, arbutin, kojic acid and its derivatives, vitamin C,vitamin E, vitamin A and their derivatives, boldine and its derivatives,licorice extract, citrus extract, bearberry extract, orange extract,lemon extract, cucumber extract, mulberry extract, rosemary extract,hops extract, mercaptosuccinic acid, mercaptodextran, glutathione,cysteine and its derivatives such as N-acetyl-L-cysteine, tocopherols,retinol, retinoic acid and retinaldehyde, and mixtures thereof.
 23. Thecosmetic composition of claim 17, which is in the form of a solution,dispersion, emulsion, paste, or powder, alone or in a premix; inmacrocapsules, microcapsules, or nanocapsules, macrospheres,microspheres or nanospheres, liposomes, oleosomes or chylomicrons,macroparticles, microparticles, or nanoparticles or macrosponges,microsponges or nanosponges; or adsorbed on organic polymer powders,talcs, bentonites, or other inorganic or organic supports.
 24. Thecomposition of claim 17, which is in the form of a cream, lotion,ointment, milk, gel, emulsion, dispersion, solution, suspension,cleanser, foundation, anhydrous preparation, body and bath oil, showerand bath gel, shampoo and scalp treatment lotion, cream or lotion forcare of the skin or hair, sun-screen lotion, milk or cream, artificialsuntan lotion, cream or milk, shaving cream or foam, aftershave lotion,make-up, mascara or nail varnish, lipstick, skin “essence,” serum,adhesive or absorbent material, transdermal patch, powder, emollientlotion, emollient milk, emollient cream, spray, foundation tint base,pomade, colloid, compact or solid suspension, pencil, sprayableformulation, or brossable.
 25. A method of decreasing skin pigmentation,whitening or bleaching human skin, lightening skin complexion,attenuating senile lentigo, homogenizing skin color, preventing orreducing melanogenesis, reducing coloration on exposure to natural orartificial UV radiation, treating or preventing cutaneoushyperpigmentation, melasma, chloasma, or freckles comprising: the stepof applying to the skin of a human in need thereof, a safe and effectiveamount of at least one peptide comprising at least one immobilizedaromatic cycle of the formula (I): A-(Xa)m-Xc-(Xb)n-B; wherein A is H,or an N-acyl group, selected from the group consisting of biotin or analkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar or an alkoxy chain,B is OR¹ or NR²R³, in which R¹, R² and R³ are, independently of eachother, H or an alkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar oralkoxy chain, “m” and “n” are between 0 and 5 with the proviso thatm+n≦5, (Xa) and (Xb) are amino acid residues, which may be the same ordifferent, genetically encoded or not encoded, and (Xa)m and (Xb)n arechains from 0 to 5 amino acids (Xa1, Xa2, Xa3, Xa4, Xa5) (Xb1, Xb2, Xb3,Xb4, Xb5) which may be the same or different genetically encoded or notencoded, with the proviso that m+n≦5, Xc is an aromatic amino acid,wherein if Xa1=His and n=0, then Xc is an amino acid residue selectedfrom the group consisting of L- or D-Trp, L- or D-Phe, L- or D-Tyr, L-or D-Tic, L- or D-7-hydroxy-Tic, or L- or D-Tpi, and Xa2 is not Ser,Ala, Phe or homoPhe; if Xa1=L-Tyr, m≦3 and n≦1, then Xc is an amino acidresidue selected among L- or D-Trp, L- or D-Phe, L- or D-Tyr, L- orD-Tic, L- or D-7-hydroxy-Tic, or L- or D-Tpi; and if Xa1 is not Tyr andnot His, m+n≦5, then Xc is an amino acid residue selected among L- orD-Tic, or L- or D-7-hydroxy-Tic, or L- or D-Tpi.
 26. The method of claim25, wherein if Xa1=His, then Xa2 is Leu.
 27. The method of claim 25,wherein the peptide is selected from the group consisting of analogs orfragments of enkephalin or endothelin.
 28. The method of claim 25,wherein the N-acyl group is selected from the group consisting ofacetyl, palmitoyl, elaidoyl, myristoyl, biotinyl, and octanoyl.
 29. Themethod of claim 25, wherein said peptide is present at a concentrationbetween 0.00001% (w/w) and 100% (w/w).
 30. The method of claim 29,wherein said peptide is present at a concentration between 0.0001% (w/w)and 20% (w/w).
 31. The method of claim 30, wherein said peptide ispresent at a concentration between 0.001% and 5% (w/w) by weight of thecomposition.
 32. A method of reducing at least one sign of agingcomprising the step of applying to a portion of human skin in needthereof, a safe and effective amount of at least one peptide comprising:providing at least one peptide comprising at least one immobilizedaromatic cycle of the formula (I): A-(Xa)m-Xc-(Xb)n-B; wherein A is H,or an N-acyl group, selected from the group consisting of biotin or analkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar or an alkoxy chain,B is OR¹ or NR²R³, in which R¹, R² and R³ are, independently of eachother, H or an alkyl, aryl, aralkyl, acyl, alcohol, sulfonyl, sugar oralkoxy chain, “m” and “n” are between 0 and 5 with the proviso thatm+n≦5, (Xa) and (Xb) are amino acid residues, which may be the same ordifferent, genetically encoded or not encoded, and (Xa)m and (Xb)n arechains from 0 to 5 amino acids (Xa1, Xa2, Xa3, Xa4, Xa5) (Xb1, Xb2, Xb3,Xb4, Xb5) which may be the same or different genetically encoded or notencoded, with the proviso that m+n≦5, Xc is an aromatic amino acid,wherein if Xa1=His and n=0, then Xc is an amino acid residue selectedfrom the group consisting of L- or D-Trp, L- or D-Phe, L- or D-Tyr, L-or D-Tic, L- or D-7-hydroxy-Tic, or L- or D-Tpi, and Xa2 is not Ser,Ala, Phe or homoPhe; if Xa1=L-Tyr, m≦3 and n≦1, then Xc is an amino acidresidue selected among L- or D-Trp, L- or D-Phe, L- or D-Tyr, L- orD-Tic, L- or D-7-hydroxy-Tic, or L- or D-Tpi; and if Xa1 is not Tyr andnot His, m+n≦5, then Xc is an amino acid residue selected among L- orD-Tic, or L- or D-7-hydroxy-Tic, or L- or D-Tpi; and applying at leastonce a day for a period of time at least sufficient to provide areduction in the visible signs of aging to the skin of a human in needthereof.
 33. The method of claim 32, wherein if Xa1=His, then Xa2 isLeu.
 34. The method of claim 32, wherein the peptide is selected fromthe group consisting of analogs or fragments of enkephalin orendothelin.
 35. The method of claim 32, wherein the N-acyl group isselected from the group consisting of acetyl, palmitoyl, elaidoyl,myristoyl, biotinyl, and octanoyl.
 36. The method of claim 32, whereinsaid peptide is present at a concentration between 0.00001% (w/w) and1000 (w/w).
 37. The method of claim 36, wherein said peptide is presentat a concentration between 0.0001% (w/w) and 20% (w/w).
 38. The methodof claim 37, wherein said peptide is present at a concentration between0.001% and 5% (w/w) by weight of the composition.